Abstract
This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN ≥ 0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt ≥ 30 x 109/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0.07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.
| Original language | English |
|---|---|
| Pages (from-to) | 23-29 |
| Number of pages | 7 |
| Journal | Bone Marrow Transplantation |
| Volume | 26 |
| Issue number | 1 |
| Publication status | Published - 2000 |
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Keywords
- Bone marrow transplantation
- Cytomegalovirus
- Foscarnet
ASJC Scopus subject areas
- Hematology
- Transplantation
Cite this
Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT) : A dose-finding study. / Bregante, S.; Bertilson, S.; Tedone, E.; Van Lint, M. T.; Trespi, G.; Mordini, N.; Berisso, G.; Gualandi, F.; Lamparelli, T.; Figari, O.; Benvenuto, F.; Raiola, A. M.; Bacigalupo, A.
In: Bone Marrow Transplantation, Vol. 26, No. 1, 2000, p. 23-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT)
T2 - A dose-finding study
AU - Bregante, S.
AU - Bertilson, S.
AU - Tedone, E.
AU - Van Lint, M. T.
AU - Trespi, G.
AU - Mordini, N.
AU - Berisso, G.
AU - Gualandi, F.
AU - Lamparelli, T.
AU - Figari, O.
AU - Benvenuto, F.
AU - Raiola, A. M.
AU - Bacigalupo, A.
PY - 2000
Y1 - 2000
N2 - This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN ≥ 0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt ≥ 30 x 109/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0.07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.
AB - This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN ≥ 0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt ≥ 30 x 109/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0.07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.
KW - Bone marrow transplantation
KW - Cytomegalovirus
KW - Foscarnet
UR - http://www.scopus.com/inward/record.url?scp=20244373137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20244373137&partnerID=8YFLogxK
M3 - Article
C2 - 10918402
AN - SCOPUS:20244373137
VL - 26
SP - 23
EP - 29
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 1
ER -