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National Survey of Use of Mesna for the Prevention of Cyclophosphamide-Induced Hemorrhagic Cystitis in Recipients of Bone Marrow Transplants
Letters Barium Enema Study Dr. MacCarty made a valid point in his article "Colorectal Cancer: The Case for Barium Enema," which was published in the March 1992 issue of the Mayo Clinic Proceedings (pages 253 to 257), when he recommended a barium contrast study as the first procedure to be used in the detection of neoplasms of the lower bowel. As a gastroenterologist, I agree that high-quality radiography is essentially equal to endoscopy in the detection of colonic polyps and cancer and that endoscopists are frequently unable, for technical reasons, to reach the upper right aspect of the colon and cecum. One unmentioned weakness in his report, however, has troubled me recently; today's residents in radiology are not nearly as well trained in performing "high-quality" barium enema examinations as their predecessors were. Because trainees are attracted to computed tomography, magnetic resonance imaging, ultrasonography, positron emission tomographic scanning, and invasive procedures, they receive progressively less education in older, reliable procedures such as barium contrast studies. Apparently, the field of diagnostic radiology of both the lower and upper portions of the digestive tract is being abdicated, inasmuch as referring physicians first think of endoscopy for their patients with suspected alimentary disorders. Medical students rarely see the results of barium enema studies; instead, they are "nourished" on endoscopic reports and illustrations, the latter of which are doubtless "prettier" than roentgenograms. Radiologic studies are indeed less dear and more comfortable than are endoscopic procedures, and neither sedatives nor analgesics are needed. In expert hands, they provide useful diagnostic information. I fear, however, that unless Dr. MacCarty and his peers do more to improve the training of their residents in these "ancient" procedures, these methods may wither on the vine and disappear. Harvey J. Dworken, M.D. Division of Gastroenterology, Emeritus University Hospitals of Cleveland Cleveland, Ohio
The author replies I thank Dr. Dworken for his kind and provocative letter. He has astutely, and correctly, observed that the rapid development and deployment of new technologies in medical imaging have diverted the attention and interest of young radiologists from the older technologies, including barium enema Mayo Clin Proc 67:611-612, 1992
studies. An equally worrisome trend is the decreasing number of barium enema examinations being performed in many university training centers. This factor can be attributed to the increased use of endoscopy as well as to the strong shift of medical care from the inpatient to the outpatient setting, where resident rotations are lacking in many training programs. The resultant decrease in skills and knowledge among young radiologists in some traditional areas of medical imaging is cause for concern. This point has been the emphasis of examining members of the American Board of Radiology, has been the focus of many discussions at the annual meetings of the Society of Gastrointestinal Radiologists, and has been the subject of numerous major presentations at national meetings on radiology. Directors of radiology training programs throughout the United States will be faced with a major challenge if enthusiasm builds for screening segments of the population for colorectal neoplasms with use of barium enema studies. My concern is not that these "ancient" (and elegant) procedures will "wither ... and disappear" but rather that the radiologic community will find itself understaffed and ill prepared to meet the challenge. Robert L. MacCarty, M.D.
National Survey of Use of Mesna for the Prevention of Cyclophosphamide-Induced Hemorrhagic Cystitis in Recipients of Bone Marrow Transplants We read with interest the editorial by Dr. Armitage, which was published in the February 1992 issue of the Mayo Clinic Proceedings (pages 195 to 197), especially the section on hemorrhagic cystitis (HC). The author mentioned several studies that describe the utility of mesna for the prevention of cyclophosphamide (CY)-induced HC; however, because of the effectiveness of hydration with forced diuresis with or without bladder irrigation, the additional costs of mesna, and the concerns about potential failures of engraftment, I the use of mesna remains controversial. Additionally, the author stated that mesna should be the standard therapy; this statement contradicts the results presented by Letendre and associates.? We have also internally discussed what should be considered the standard practice for the prevention of He. In attempts to obtain this information, we recently conducted a national survey on the use of mesna for the preventionof CY-induced HC in patients who undergo bone marrow transplantation. 611
612
Mayo Clin Proc, June 1992, Vol 67
LETTERS
Briefly, a questionnaire, which consisted of four multiple-part questions, was mailed during the period January to March 1991 to 76 centers listed in the 1990 edition of the Bone Marrow Transplant Nursing Resource Directory. The surveys were categorized by the type of bone marrow transplantation performed, the preparatory chemotherapeutic regimen, and the geographic location of the center. The prevention of HC was classified on the basis of the use of mesna, intravenous hydration, local bladder irrigation, and combinations of these strategies. Of the 76 mailed surveys, 52 (68%) were completed and returned. The regional response was 10 from the Northeast, 15 from the North Central, 16 from the South, and 11 from the West. One survey was excluded because the institution did not use CY in the preparatory regimen. Of the 51 institutions, 20% performed autologous bone marrow transplantation only, 6% allogeneic transplantation only, and 74% both techniques. Various preparatory regimens that contained CY were used on the basis of the specific disease state, institution, and transplantation technique. Because of this variation, regimens were characterized only by cv, busulfan, and totalbody irradiation (TBI) usage as follows: CY + busulfan + TBI (37%); CY + busulfan but no TBI (29%); CY + TBI but no busulfan (20%); and CY only (14%). In most cases, other chemotherapeutic agents were added to these regimens. Of the 51 institutions, 28 (55%) used mesna in various regimens: 23 (45%) used mesna plus intravenous hydration, 4 (8%) used mesna plus intravenous hydration plus bladder irrigation, and 1 (2%) used only mesna. Intermittent bolus dosing was used by 61 % of the institutions, whereas continuous infusion was used by the rest (Tables 1 and 2). In 23 of the institutions (45%), mesna was not used; 11 (48%) used intravenous hydration alone, and 12 (52%) combined intravenous hydration with bladder irrigation. Overall, intravenous hydration was used in 50 of the 51 institutions. Although various rates of intravenous hydration were used, 80% of the institutions used from 150 to 250 ml/h. Most
20 20 20 40 Miscellaneous
Institutions Dose*
No.
%
80 100 140 160 Miscellaneous
1 6 1 I 2
9 55 9 9 18
*Percentage of dose of cyclophosphamide infused per day for duration of cyclophosphamide therapy.
institutions (82%) continued the chosen rate of hydration for 24 hours after the last dose of CY. The last section of the survey focused on the reasons for not using mesna. Of the 23 institutions that did not use mesna, 21 provided 31 reasons, including the following: availability of other effective methods (45%), concern about the related effects of mesna on engraftment (20%), and additional costs (13%). Another 20% were evenly divided between insufficient data or unknown side effects and the fact that mesna was not currently part of the specific protocol at their site. One institution cited previous treatment failures with maximal doses of mesna. At the time the survey was conducted, 55% of the responding institutions used mesna for the prevention of CYinduced HC in patients who undergo bone marrow transplantation. Although our survey does not address the individual controversial aspects of this preventive therapy, it provides clinicians with national insight into the standard practice. David P. Nicolau, Pharm.D. Department of Hospital Pharmacy Hartford Hospital Hartford, Connecticut Kathy R. Hogan, Pharm.D. Department of Hospital Pharmacy Practice and Administration Medical University of South Carolina Charleston, South Carolina
Table I.-Intermittent Bolus Dosing Regimens of Mesna Used at 17 Institutions That Perform Bone Marrow Transplantation Dose*
Table 2.-Continuous Infusion Regimens of Mesna Used at 11 Institutions That Perform Bone Marrow Transplantation
Institutions
No. of dosesj
Dose/day*
No.
%
3 4 5 4
60 80 100 160
2 3 6 3 3
12 18 35 18 18
*Percentage of dose of cyclophosphamide. [Doses per day for duration of cyclophosphamide therapy.
REFERENCES 1. Hows JM, Mehta A, Ward L, Woods K, Perez R, Gordon MY, Gordon-Smith EC: Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study. Br J Cancer 50:753-756, 1984 2. Letendre L, Hoagland HC, Gertz MA: Hemorrhagic cystitis complicating bone marrow transplantation. Mayo Clin Proc 67:128-130, 1992
The author replies I thank Dr. Dworken for his kind and provocative letter. He has astutely, and correctly, observed that the rapid development and deployment of new technologies in medical imaging have diverted the attention and interest of young radiologists from the older technologies, including barium enema Mayo Clin Proc 67:611-612, 1992
studies. An equally worrisome trend is the decreasing number of barium enema examinations being performed in many university training centers. This factor can be attributed to the increased use of endoscopy as well as to the strong shift of medical care from the inpatient to the outpatient setting, where resident rotations are lacking in many training programs. The resultant decrease in skills and knowledge among young radiologists in some traditional areas of medical imaging is cause for concern. This point has been the emphasis of examining members of the American Board of Radiology, has been the focus of many discussions at the annual meetings of the Society of Gastrointestinal Radiologists, and has been the subject of numerous major presentations at national meetings on radiology. Directors of radiology training programs throughout the United States will be faced with a major challenge if enthusiasm builds for screening segments of the population for colorectal neoplasms with use of barium enema studies. My concern is not that these "ancient" (and elegant) procedures will "wither ... and disappear" but rather that the radiologic community will find itself understaffed and ill prepared to meet the challenge. Robert L. MacCarty, M.D.
National Survey of Use of Mesna for the Prevention of Cyclophosphamide-Induced Hemorrhagic Cystitis in Recipients of Bone Marrow Transplants We read with interest the editorial by Dr. Armitage, which was published in the February 1992 issue of the Mayo Clinic Proceedings (pages 195 to 197), especially the section on hemorrhagic cystitis (HC). The author mentioned several studies that describe the utility of mesna for the prevention of cyclophosphamide (CY)-induced HC; however, because of the effectiveness of hydration with forced diuresis with or without bladder irrigation, the additional costs of mesna, and the concerns about potential failures of engraftment, I the use of mesna remains controversial. Additionally, the author stated that mesna should be the standard therapy; this statement contradicts the results presented by Letendre and associates.? We have also internally discussed what should be considered the standard practice for the prevention of He. In attempts to obtain this information, we recently conducted a national survey on the use of mesna for the preventionof CY-induced HC in patients who undergo bone marrow transplantation. 611
612
Mayo Clin Proc, June 1992, Vol 67
LETTERS
Briefly, a questionnaire, which consisted of four multiple-part questions, was mailed during the period January to March 1991 to 76 centers listed in the 1990 edition of the Bone Marrow Transplant Nursing Resource Directory. The surveys were categorized by the type of bone marrow transplantation performed, the preparatory chemotherapeutic regimen, and the geographic location of the center. The prevention of HC was classified on the basis of the use of mesna, intravenous hydration, local bladder irrigation, and combinations of these strategies. Of the 76 mailed surveys, 52 (68%) were completed and returned. The regional response was 10 from the Northeast, 15 from the North Central, 16 from the South, and 11 from the West. One survey was excluded because the institution did not use CY in the preparatory regimen. Of the 51 institutions, 20% performed autologous bone marrow transplantation only, 6% allogeneic transplantation only, and 74% both techniques. Various preparatory regimens that contained CY were used on the basis of the specific disease state, institution, and transplantation technique. Because of this variation, regimens were characterized only by cv, busulfan, and totalbody irradiation (TBI) usage as follows: CY + busulfan + TBI (37%); CY + busulfan but no TBI (29%); CY + TBI but no busulfan (20%); and CY only (14%). In most cases, other chemotherapeutic agents were added to these regimens. Of the 51 institutions, 28 (55%) used mesna in various regimens: 23 (45%) used mesna plus intravenous hydration, 4 (8%) used mesna plus intravenous hydration plus bladder irrigation, and 1 (2%) used only mesna. Intermittent bolus dosing was used by 61 % of the institutions, whereas continuous infusion was used by the rest (Tables 1 and 2). In 23 of the institutions (45%), mesna was not used; 11 (48%) used intravenous hydration alone, and 12 (52%) combined intravenous hydration with bladder irrigation. Overall, intravenous hydration was used in 50 of the 51 institutions. Although various rates of intravenous hydration were used, 80% of the institutions used from 150 to 250 ml/h. Most
20 20 20 40 Miscellaneous
Institutions Dose*
No.
%
80 100 140 160 Miscellaneous
1 6 1 I 2
9 55 9 9 18
*Percentage of dose of cyclophosphamide infused per day for duration of cyclophosphamide therapy.
institutions (82%) continued the chosen rate of hydration for 24 hours after the last dose of CY. The last section of the survey focused on the reasons for not using mesna. Of the 23 institutions that did not use mesna, 21 provided 31 reasons, including the following: availability of other effective methods (45%), concern about the related effects of mesna on engraftment (20%), and additional costs (13%). Another 20% were evenly divided between insufficient data or unknown side effects and the fact that mesna was not currently part of the specific protocol at their site. One institution cited previous treatment failures with maximal doses of mesna. At the time the survey was conducted, 55% of the responding institutions used mesna for the prevention of CYinduced HC in patients who undergo bone marrow transplantation. Although our survey does not address the individual controversial aspects of this preventive therapy, it provides clinicians with national insight into the standard practice. David P. Nicolau, Pharm.D. Department of Hospital Pharmacy Hartford Hospital Hartford, Connecticut Kathy R. Hogan, Pharm.D. Department of Hospital Pharmacy Practice and Administration Medical University of South Carolina Charleston, South Carolina
Table I.-Intermittent Bolus Dosing Regimens of Mesna Used at 17 Institutions That Perform Bone Marrow Transplantation Dose*
Table 2.-Continuous Infusion Regimens of Mesna Used at 11 Institutions That Perform Bone Marrow Transplantation
Institutions
No. of dosesj
Dose/day*
No.
%
3 4 5 4
60 80 100 160
2 3 6 3 3
12 18 35 18 18
*Percentage of dose of cyclophosphamide. [Doses per day for duration of cyclophosphamide therapy.
REFERENCES 1. Hows JM, Mehta A, Ward L, Woods K, Perez R, Gordon MY, Gordon-Smith EC: Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study. Br J Cancer 50:753-756, 1984 2. Letendre L, Hoagland HC, Gertz MA: Hemorrhagic cystitis complicating bone marrow transplantation. Mayo Clin Proc 67:128-130, 1992