CORRESPONDENCE
grounds, and are likely to go untreated until the results of blood cultures are available. This emphasizes the importance of performing blood cultures in patients with suspected sepsis. JAMES W. GRAY
University of Newcastle upon Tyne STEPHEN J. PEDLER
Royal Victoria Infirmary Newcastle upon Tyne United Kingdom 1. Lombardi DP. Engleberg NC. Anaerobic bacteremia: incidence, patient characteristics, and dinical significance. Am J Med 1992; 92: 53-60. 2. Dorsher CW. Rosenblatt JE. Wilson WR. llstrup DM. Anaerobic bacteremia: decreasing rate over a E-year period. Rev Infect Dis 1991; 13: 633-6. 3. Gransden WR. Eykyn SJ. Phillips I. Anaerobic bacteremia: declining rate over a E-year period. Rev Infect Dis 1991; 13: 1255-6. Submitted
April 1, 1992. and accepted
May 25. 1992
The Reply: In Gray and Pedler’s analysis, one third (6 of 18 cases) of anaerobic bacteremias occurred in patients who had no clinically obvious source of infection; 4 of these cases occurred in febrile, neutropenic patients. In our study, only 5 of the 40 cases were of uncertain origin, 2 being in febrile, neutropenic patients. The differences seem striking, but the numbers of cases are small, and the relative proportions of bacteremias from uncertain sources are not statistically different (p = 0.0% Fisher’s exact test, two-tailed). Although this trend may reflect a real difference, the patient populations and medical practices in the two study locations may be different in ways that would affect the local epidemiology of anaerobic bacteremia. Our colleagues’ judgment that seven of their patients would not have received antianaerobic therapy without the benefit of the blood culture result led them to reaffirm the importance of culturing blood for obligate anaerobes. We found that the results of anaerobic blood cultures rarely influenced patient management, although the empiric use of ex-
tended-spectrum antibiotics (e.g., ticarcillin-clavulanate or imipenem/cilastatin) in some of our cases leaves us uncertain as to whether the inclusion of antianaerobic activity was by design or by default. In part because of the use of these antibiotics, there were no cases in our study in which the isolation of an anaerobe was both unexpected and influential in management. Nevertheless, while there may be specific clinical circumstances in which dedicated anaerobic cultures can reasonably be omitted from the blood culture routine, we agree that the clinical situations emphasized by Gray and Pedler, i.e., fever with neutropenia and fever without an obvious source of infection, are circumstances in which anaerobic blood culture techniques are clearly indicated. N. CARY ENGLEBERG,
M.D.
University of Michigan Medical School Ann Arbor, Michigan DONALD P. LOMBARDI, M.D.
Bethesda Naval Hospital Bethesda, Maryland
ACUTE MYELOGENOUS LEUKEMIA TO the Editor:
I enjoyed reading the recent review of acute myelogenous leukemia (AML) by Mastrianni et al [l]. However, I disagree with some of their statements, as follows: (1) Although it is difficult to estimate the incidence of AML, the 10,000 cases per year figure is not supported by their reference. The American Cancer Society estimates that 11,300 cases of granulocytic leukemia will be diagnosed in the United States in 1992 [2]; however, only about 77% of these cases will be AML (the rest is accounted by chronic myelogenous leukemia) [3]. The es-
Decrmkr
timated incidence of AML is thus closer to 8,700 cases per year. (2) Allogeneic bone marrow transplantation is somewhat riskier but still potentially lifesaving and feasible in patients over 45 [4-6]. Many centers (including ours) perform transplants in such patients. The blanket statement “the procedure is used only for patients under 45 years old” is inaccurate, and adherence to such a rule may prevent curative therapy in many patients. (3) It is misleading to label p53 as an antioncogene (i.e., a gene that prevents malignant transformation when present) in AML. The study by Smith et al [7] quoted in the article actually showed a positive correlation between ~53 protein expression and secondary plating efficiency, an indicator of poor prognosis in AML [S]. We have recently reported that inhibition of ~53 RNA with an antisense oligonucleotide suppresses in vitro growth of fresh AML cells [9]. It would be more accurate to say that ~53 is involved in leukemogenesis, and that reversal of this action may be clinically useful in the future. JORGE A. SPINOLO, MB.
University of Nebraska Medical Center Omaha, Nebraska 1. Mastrianni DM. Tung NM. Tenen DG. Acute myelogenous leukemia: current treatment and future directions. Am J Med 1992; 92: 286-95. 2. Boring CC, Squires TS, Tong T. Cancer statistics, 1992. CA 1992; 42: 19-36. 3. Jandl JH. Blood: textbook of hematology. Boston: Little Brown, 1987: 633. 4. Klingemann HG. Storb R. Fefer A. et a/. Bone marrow transplantation in patients aged 45 years and older. Blood 1986; 67: 770-6. 5. Blume KG, Forman SJ, Nademanee AP, et a/. Bone marrow transplantation for hematologic ma lignandes in patients aged 30 years or older. J Clin Oncol 1986; 4: 1489-92. 6. Copafan EA. Kapoor N, Berliner M. Tutschka PJ. Bone marrow transplantation without total-body irradiation in patients aged 40 and older. Transplantation 1989; 48: 65-3. 7. Smith LJ. McCulloch EA. Benchimol S. Expression of the ~53 oncogene
1992 The American Journal of Medicine
in acute myeloblastic
leu-
Volume 93
707
CORRESPONDENCE
of ~53 appear to lead to inactivation of the wild-type gene that normally suppresses tumor formation-hence the common designation of ~53 as an “antioncogene” [8]. In different patient8 with AML, mutations of ~53 may be involved in leukemogenesia, reflect severe genetic instability, or simply be an epiphenomenon. Because the role of p53 in AML is not fully understood, Dr. Spino10’8 caveat in using the common label of ~53 as an “antioncogene” in AML is noted.
the patient’s past medical history. The answer is obviously a qualified, ‘yes.’ In fact, the cases in which a 1984; 2: 253-9. judgment was made as to the util9. Dlcke KA. Bayever E, Yao Y, et a/. Antisense p53 ity in case management of having oliionucleotides: potential antileukemic agents [ab an old ECG are shown in Table &act]. Blood 1991; 78 Suppl 1: 383a. IV of Ziemba et al’s article. The Submitted February 28, 1992, and accepted June author8 suggest that availability 11,1992 of baseline ECGs benefited the patient in five of eight cases (PaThe Reply: tients 3, 4, 5, 6, and 8). My own We agree with Dr. Spinolo that it review suggests that the cases of is difficult to estimate the inciPatients 4 and 8, both of which dence of AML in the U.S. As ilshowed that left bundle branch lustration, we note that Dr. SpinDAVID M. MASTRIANNI, MB. block was not present on prior NADINE M. TUNG, M.D. ECGs, were the cases of utility. 010’s calculation of 8,700 cases DANIEL G. TENEN, M.D. per year differ8 from the 11,000 The others either showed atrial Beth Israel Hospital cases per year calculated by one Boston, Massachusetts fibrillation (AF), ischemia, or of the author8 he reference8 [l]. ventricular tachycardia, all of 1. Jandl JH. Blood: textbook of hematology. BosWe believe reporting the inciton: Little Brown, 1987: 633. which, in the presence of symp2. Clii RA. Buckner CD, Thomas ED, eta/. The treatdence of AML as “approximately toms, would have been enough to ment of acute nonlymphoblastic leukemia by alloge10,000 patients” per year avoids admit for treatment or monitorneic transplantation. Bone Marrow Transplant implying precision in what is cer- 1987; 2: 243-8. ing. The rates of AF and the he3. Klingemann HG. Storb R, Fefer A, et al. Bone tainly an inaccurate reporting modynamic and clinical consemarrow transplantation in patients aged 45 years system and provides the reader quences at the time of the ED and older. Blood 1986; 67: 770-6. with a convenient figure to use in 4. Hsu IC, Metcalf RA, Sun T. et al. Mutational hot- evaluation would be more imporcomparing the incidence of AML tant to me than the presence or spot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 3501 427-8. with other diseases. absence of similar finding8 in the The role of allogeneic bone 5. Baker SJ. Fearon ER. Nigro JM, et a/. Chromopast. (The ventricular rates and somes 17 deletions and p53 gene mutations in colomarrow transplantation in the rectal carcinomas. Science 1989; 244: 217-21. blood pressures in AF are not givtreatment of AML remains con- 6. Nigro JM, Baker SJ. Preisinger AC, et a/. Muta- en.) troversial. We have attempted to tions in the p53 gene occur in diverse human tuCertain situations in which a types. Nature 1989; 342: 705-8. present a balanced view of the 7.mourTakahashi prior ECG would be most helpful T. Nau NM, Chiba I, et al. ~53: a frebenefit8 and toxicities of this pro- quent target for genetic abnormalities in lung can- were not encountered: chronic cedure. The toxicity of allogeneic cer. Science 1989; 246: 4914. ST elevation of an old aneurysm bone marrow transplantation in- 8. Finlay CA, Hinds PW, Levine Al. The p53 proto(unless this is what is meant by oncogene can act as a suppressor of transformacreases with age, and the proce- tion. ‘ischemic changes’) or early repoCell 1989; 57: 1083-93. dure is most appropriate for palarization, frequent premature tients under age 45. While an ocventricular contractions, poor Rcasional highly selected patient wave progression, left anterior over the age of 45 will undergo fascicular block (resembling infeIN allogeneic transplantation, the ELECTROCARDIOGRAMS rior infarction and/or anterosepELDERLYPATIENTS IN THE poor reported results and high tal myocardial infarction), EMERGENCYDEPARTMENT toxicity preclude allogeneic marked change in axis, and so transplantation as standard care To the Editor: forth. for the vast majority of older pa- The article by Ziemba et al [l] is By the time someone is 65 or tients [2,3]. fundamentally superfluous. It older and living in a care facility Mutations of the ~53 gene have asks the question of whether a for the elderly, he or she will have been reported in multiple human physician is better off evaluating surely had an ECG, and in my malignancies [4] such as colorecelderly patients in an emergency opinion it is quite appropriate to tal [5], hepatocellular [6], and department (ED) setting with make it available with the rest of lung [7] carcinoma as well a8 in more (i.e., prior electrocardiothe medical record, on each occahematologic malignancies such as gram [ECG]) rather than less sion that a patient come8 to the AML. In most models, mutations (i.e., no prior ECG) data about local ED. Not to do 80 would be kemia. J Exp Med 1986; 1641 75161. 6.Curtis JE. Messner HA, Has&back R, Elhakim TM. McCulloch EA. Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia. J Clin Oncol
708
December 1992 The American Journal of Medlclne
Volume 93
grounds, and are likely to go untreated until the results of blood cultures are available. This emphasizes the importance of performing blood cultures in patients with suspected sepsis. JAMES W. GRAY
University of Newcastle upon Tyne STEPHEN J. PEDLER
Royal Victoria Infirmary Newcastle upon Tyne United Kingdom 1. Lombardi DP. Engleberg NC. Anaerobic bacteremia: incidence, patient characteristics, and dinical significance. Am J Med 1992; 92: 53-60. 2. Dorsher CW. Rosenblatt JE. Wilson WR. llstrup DM. Anaerobic bacteremia: decreasing rate over a E-year period. Rev Infect Dis 1991; 13: 633-6. 3. Gransden WR. Eykyn SJ. Phillips I. Anaerobic bacteremia: declining rate over a E-year period. Rev Infect Dis 1991; 13: 1255-6. Submitted
April 1, 1992. and accepted
May 25. 1992
The Reply: In Gray and Pedler’s analysis, one third (6 of 18 cases) of anaerobic bacteremias occurred in patients who had no clinically obvious source of infection; 4 of these cases occurred in febrile, neutropenic patients. In our study, only 5 of the 40 cases were of uncertain origin, 2 being in febrile, neutropenic patients. The differences seem striking, but the numbers of cases are small, and the relative proportions of bacteremias from uncertain sources are not statistically different (p = 0.0% Fisher’s exact test, two-tailed). Although this trend may reflect a real difference, the patient populations and medical practices in the two study locations may be different in ways that would affect the local epidemiology of anaerobic bacteremia. Our colleagues’ judgment that seven of their patients would not have received antianaerobic therapy without the benefit of the blood culture result led them to reaffirm the importance of culturing blood for obligate anaerobes. We found that the results of anaerobic blood cultures rarely influenced patient management, although the empiric use of ex-
tended-spectrum antibiotics (e.g., ticarcillin-clavulanate or imipenem/cilastatin) in some of our cases leaves us uncertain as to whether the inclusion of antianaerobic activity was by design or by default. In part because of the use of these antibiotics, there were no cases in our study in which the isolation of an anaerobe was both unexpected and influential in management. Nevertheless, while there may be specific clinical circumstances in which dedicated anaerobic cultures can reasonably be omitted from the blood culture routine, we agree that the clinical situations emphasized by Gray and Pedler, i.e., fever with neutropenia and fever without an obvious source of infection, are circumstances in which anaerobic blood culture techniques are clearly indicated. N. CARY ENGLEBERG,
M.D.
University of Michigan Medical School Ann Arbor, Michigan DONALD P. LOMBARDI, M.D.
Bethesda Naval Hospital Bethesda, Maryland
ACUTE MYELOGENOUS LEUKEMIA TO the Editor:
I enjoyed reading the recent review of acute myelogenous leukemia (AML) by Mastrianni et al [l]. However, I disagree with some of their statements, as follows: (1) Although it is difficult to estimate the incidence of AML, the 10,000 cases per year figure is not supported by their reference. The American Cancer Society estimates that 11,300 cases of granulocytic leukemia will be diagnosed in the United States in 1992 [2]; however, only about 77% of these cases will be AML (the rest is accounted by chronic myelogenous leukemia) [3]. The es-
Decrmkr
timated incidence of AML is thus closer to 8,700 cases per year. (2) Allogeneic bone marrow transplantation is somewhat riskier but still potentially lifesaving and feasible in patients over 45 [4-6]. Many centers (including ours) perform transplants in such patients. The blanket statement “the procedure is used only for patients under 45 years old” is inaccurate, and adherence to such a rule may prevent curative therapy in many patients. (3) It is misleading to label p53 as an antioncogene (i.e., a gene that prevents malignant transformation when present) in AML. The study by Smith et al [7] quoted in the article actually showed a positive correlation between ~53 protein expression and secondary plating efficiency, an indicator of poor prognosis in AML [S]. We have recently reported that inhibition of ~53 RNA with an antisense oligonucleotide suppresses in vitro growth of fresh AML cells [9]. It would be more accurate to say that ~53 is involved in leukemogenesis, and that reversal of this action may be clinically useful in the future. JORGE A. SPINOLO, MB.
University of Nebraska Medical Center Omaha, Nebraska 1. Mastrianni DM. Tung NM. Tenen DG. Acute myelogenous leukemia: current treatment and future directions. Am J Med 1992; 92: 286-95. 2. Boring CC, Squires TS, Tong T. Cancer statistics, 1992. CA 1992; 42: 19-36. 3. Jandl JH. Blood: textbook of hematology. Boston: Little Brown, 1987: 633. 4. Klingemann HG. Storb R. Fefer A. et a/. Bone marrow transplantation in patients aged 45 years and older. Blood 1986; 67: 770-6. 5. Blume KG, Forman SJ, Nademanee AP, et a/. Bone marrow transplantation for hematologic ma lignandes in patients aged 30 years or older. J Clin Oncol 1986; 4: 1489-92. 6. Copafan EA. Kapoor N, Berliner M. Tutschka PJ. Bone marrow transplantation without total-body irradiation in patients aged 40 and older. Transplantation 1989; 48: 65-3. 7. Smith LJ. McCulloch EA. Benchimol S. Expression of the ~53 oncogene
1992 The American Journal of Medicine
in acute myeloblastic
leu-
Volume 93
707
CORRESPONDENCE
of ~53 appear to lead to inactivation of the wild-type gene that normally suppresses tumor formation-hence the common designation of ~53 as an “antioncogene” [8]. In different patient8 with AML, mutations of ~53 may be involved in leukemogenesia, reflect severe genetic instability, or simply be an epiphenomenon. Because the role of p53 in AML is not fully understood, Dr. Spino10’8 caveat in using the common label of ~53 as an “antioncogene” in AML is noted.
the patient’s past medical history. The answer is obviously a qualified, ‘yes.’ In fact, the cases in which a 1984; 2: 253-9. judgment was made as to the util9. Dlcke KA. Bayever E, Yao Y, et a/. Antisense p53 ity in case management of having oliionucleotides: potential antileukemic agents [ab an old ECG are shown in Table &act]. Blood 1991; 78 Suppl 1: 383a. IV of Ziemba et al’s article. The Submitted February 28, 1992, and accepted June author8 suggest that availability 11,1992 of baseline ECGs benefited the patient in five of eight cases (PaThe Reply: tients 3, 4, 5, 6, and 8). My own We agree with Dr. Spinolo that it review suggests that the cases of is difficult to estimate the inciPatients 4 and 8, both of which dence of AML in the U.S. As ilshowed that left bundle branch lustration, we note that Dr. SpinDAVID M. MASTRIANNI, MB. block was not present on prior NADINE M. TUNG, M.D. ECGs, were the cases of utility. 010’s calculation of 8,700 cases DANIEL G. TENEN, M.D. per year differ8 from the 11,000 The others either showed atrial Beth Israel Hospital cases per year calculated by one Boston, Massachusetts fibrillation (AF), ischemia, or of the author8 he reference8 [l]. ventricular tachycardia, all of 1. Jandl JH. Blood: textbook of hematology. BosWe believe reporting the inciton: Little Brown, 1987: 633. which, in the presence of symp2. Clii RA. Buckner CD, Thomas ED, eta/. The treatdence of AML as “approximately toms, would have been enough to ment of acute nonlymphoblastic leukemia by alloge10,000 patients” per year avoids admit for treatment or monitorneic transplantation. Bone Marrow Transplant implying precision in what is cer- 1987; 2: 243-8. ing. The rates of AF and the he3. Klingemann HG. Storb R, Fefer A, et al. Bone tainly an inaccurate reporting modynamic and clinical consemarrow transplantation in patients aged 45 years system and provides the reader quences at the time of the ED and older. Blood 1986; 67: 770-6. with a convenient figure to use in 4. Hsu IC, Metcalf RA, Sun T. et al. Mutational hot- evaluation would be more imporcomparing the incidence of AML tant to me than the presence or spot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 3501 427-8. with other diseases. absence of similar finding8 in the The role of allogeneic bone 5. Baker SJ. Fearon ER. Nigro JM, et a/. Chromopast. (The ventricular rates and somes 17 deletions and p53 gene mutations in colomarrow transplantation in the rectal carcinomas. Science 1989; 244: 217-21. blood pressures in AF are not givtreatment of AML remains con- 6. Nigro JM, Baker SJ. Preisinger AC, et a/. Muta- en.) troversial. We have attempted to tions in the p53 gene occur in diverse human tuCertain situations in which a types. Nature 1989; 342: 705-8. present a balanced view of the 7.mourTakahashi prior ECG would be most helpful T. Nau NM, Chiba I, et al. ~53: a frebenefit8 and toxicities of this pro- quent target for genetic abnormalities in lung can- were not encountered: chronic cedure. The toxicity of allogeneic cer. Science 1989; 246: 4914. ST elevation of an old aneurysm bone marrow transplantation in- 8. Finlay CA, Hinds PW, Levine Al. The p53 proto(unless this is what is meant by oncogene can act as a suppressor of transformacreases with age, and the proce- tion. ‘ischemic changes’) or early repoCell 1989; 57: 1083-93. dure is most appropriate for palarization, frequent premature tients under age 45. While an ocventricular contractions, poor Rcasional highly selected patient wave progression, left anterior over the age of 45 will undergo fascicular block (resembling infeIN allogeneic transplantation, the ELECTROCARDIOGRAMS rior infarction and/or anterosepELDERLYPATIENTS IN THE poor reported results and high tal myocardial infarction), EMERGENCYDEPARTMENT toxicity preclude allogeneic marked change in axis, and so transplantation as standard care To the Editor: forth. for the vast majority of older pa- The article by Ziemba et al [l] is By the time someone is 65 or tients [2,3]. fundamentally superfluous. It older and living in a care facility Mutations of the ~53 gene have asks the question of whether a for the elderly, he or she will have been reported in multiple human physician is better off evaluating surely had an ECG, and in my malignancies [4] such as colorecelderly patients in an emergency opinion it is quite appropriate to tal [5], hepatocellular [6], and department (ED) setting with make it available with the rest of lung [7] carcinoma as well a8 in more (i.e., prior electrocardiothe medical record, on each occahematologic malignancies such as gram [ECG]) rather than less sion that a patient come8 to the AML. In most models, mutations (i.e., no prior ECG) data about local ED. Not to do 80 would be kemia. J Exp Med 1986; 1641 75161. 6.Curtis JE. Messner HA, Has&back R, Elhakim TM. McCulloch EA. Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia. J Clin Oncol
708
December 1992 The American Journal of Medlclne
Volume 93
