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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,
      • 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.
      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.
      • Letendre L
      • Hoagland HC
      • Gertz MA
      Hemorrhagic cystitis complicating bone marrow transplantation.
      We have also internally discussed what should be considered the standard practice for the prevention of HC. In attempts to obtain this information, we recently conducted a national survey on the use of mesna for the prevention of CY-induced HC in patients who undergo bone marrow transplantation.
      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 CY, busulfan, and total-body 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 (Table 1, Table 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 institutions (82%) continued the chosen rate of hydration for 24 hours after the last dose of CY.
      Table 1Intermittent Bolus Dosing Regimens of Mesna Used at 17 Institutions That Perform Bone Marrow Transplantation
      Institutions
      Dose
      Percentage of dose of cyclophosphamide.
      No. of doses
      Doses per day for duration of cyclophosphamide therapy.
      Dose/day
      Percentage of dose of cyclophosphamide.
      No.%
      20360212
      20480318
      205100635
      404160318
      Miscellaneous318
      * Percentage of dose of cyclophosphamide.
      Doses per day for duration of cyclophosphamide therapy.
      Table 2Continuous Infusion Regimens of Mesna Used at 11 Institutions That Perform Bone Marrow Transplantation
      Institutions
      Dose
      Percentage of dose of cyclophosphamide infused per day for duration of cyclophosphamide therapy.
      No.%
      8019
      100655
      14019
      16019
      Miscellaneous218
      * Percentage of dose of cyclophosphamide infused per day for duration of cyclophosphamide therapy.
      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 CY-induced 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.

      REFERENCES

        • 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. 1984; 50: 753-756
        • Letendre L
        • Hoagland HC
        • Gertz MA
        Hemorrhagic cystitis complicating bone marrow transplantation.
        Mayo Clin Proc. 1992; 67: 128-130