Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients (SOT)

1
Ten years experience of liposomal amphotericin B,
AmBisome treatment in solid organ transplant
recipients(SOT)
2
Our experience with AmBisome

• More than 10 years experience in 383 patients.
• Two double blind placebo controlled randomized
  trials with AmBisome as prophylaxis
• Allogeneic autologous BMT
• Liver transplant recipients
• Three Retrospective analyses of treatment with
  respect to safety and efficacy
• Allogeneic BMT recipients (5 years) (79 patients)
• Solid organ transplant recipients (10years) (196
  patients)
• Child recipients of transplant (7 years) (61
  patients)

3
Fungal Infections - Morbidity /Mortality

• Invasive fungal infections contribute to the
  morbidity and mortality in SOT recipients.
• Reported incidence up to 53
• Kidney 0 - 20
• Liver 4 - 42
• Pancreas 6 - 38
• Heart/lung 10 - 35
• Small bowel 33 - 53
• Reported mortality up to 77 for
  Candidosis up to 100 for Aspergillosis

4
Incidence of invasive fungal infections at our
center during the time periods 1989 to 1994 1996

• Organ n VFI Incid S FI Incid
• Liver 240 21 9 17 16
• Kidney 540 5 1 16 4
• Kidney
• Pancreas 38 1 3 9 26
• BMT 199 17 9 41 29
• VFI verified fungal infection
• SFI suspected fungal infection

5
AmBisome prophylaxis

• Liver transplant recipients
• Transplantation. 59 1 45-50, 1995.
• Transplant. Proc.27 1195-1198, 1995.

6
Study Design LTX prophylaxis

• Double blind randomized, placebo controlled study
• 86 patients were randomized
• Prophylactic treatment
• Treatment group AmBisome, 1 mg/kg daily i.v.
• Control group Equal volume of placebo drug i.v.
• Treatment during days 1 to 5 posttransplant
• Evaluation criteria for efficacy
• 77 patients who recieved all 5 days of prophylaxis

7
Results Adverse Events LTX prophylaxis all 84
patients
8
Results invasive fungal infections after
prophylaxis in LTX, first year
plt0.01
plt0.05
9
LTX prophylaxis Results early FI Placebo
group

• Invasive fungal infections
• 5 Candida albicans inf 4 peritonitis - abdomen
  cultures
• 1 fungemia - blood cultures
• 1 Aspergillus niger inf Pneumonia - BAL culture
  biopsy
• Median day to FI 12 (range 6 - 20)
• All patients recieved treatment and 5 survived

10
LTX prophylaxis Results late FI Placebo
group

• Invasive fungal infections
• 4 Candida albicans inf 1 peritonitis - abdomen
  cultures
• 3 disseminated - autopsy findings
• 1 Aspergillosis Disseminated - autopsy finding
• Median day to FI 150 (range 41 - 365)
• 2 of 5 patients recieved treatment and 1was cured

11
LTX prophylaxis Results late FI AmBisome
group

• Invasive fungal infections
• 3 Aspergillus spp inf 1 pneumonia autopsy
  findings
• 2 disseminated autopsy findings
• 1 Candida albicans Cholangitis - cultures
• Median day to FI 81 (range 39 - 325)
• 1 of 4 patients recieved treatment and was cured

12
AmBisome treatment

• Solid organ transplant recipients,
• 10 year data

13
SOT patients

• Patients treated between Jan 1989 - March 1999
• 196 solid organ transplant recipients
• 220 episodes of AmBisome treatment
• 56 for a verified infections
• 79 for a suspected infections
• 85 as prophylaxis
• 106 males
• 90 females
• Median age was 42 years, range 1 - 72

14
SOT patients

• 123 liver (LTX) transplant recipients
• 3 liver and bone marrow transplant recipients
• 5 liver and kidney transplant recipients
• 42 kidney (KTX) transplant recipients
• 21 kidney pancreas (KPTX) transplant recipients
• 1 kidney and insulin islet transplantation
  recipient
• 1 pancreas (P) transplant recipients

15
AmBisome treatment data in SOT

• Fungal Infection
• AmBisome treatment Verified Suspected Prophylact
  ic
• Duration (days),
• mean SD (median) 2317(18) 1815 (14) 1619
  (7)
• range 4-81 1-80 1-83
• Max. dose (mg),
• mean SD (median) 2.01 (1.8) 1.70.9
  (1.4) 1.40.8 (1.0 )
• range 0.7-5.5 0.7-5 0.6-6
• Total dose (g),
• mean SD (median) 1.71.7 (0.95) 1.41.3
  (1.1) 0.60.5 (0.4)
• range 0.05-8.1 0.06-8 0.03-2.4

16
Days with AmBisome
17
AmBisome dose (mg/kg/d)
18
Total dose AmBisome (gram)
19
Adverse events in SOT

• 335 adverse events were reported
• 9 (3) were regarded as caused by AmBisome
  treatment
• 6 Lumbago
• 2 Lumbago combined with chills
• 1 Lumbago with dyspnea
• No anaphylactic reaction was reported
• 224 (67) of the adverse events were regarded as
  probably related to AmBisome
• 112 (33) of the adverse events were regarded as
  not related to AmBisome

20
Kidney function before, during and after AmBisome
treatment measured as S-creatinine
21
Efficacy Suspected FI in SOT

• 75 patients recieved 79 episodes of treatment for
  suspected FI
• 57 patients survived with clearance of symptoms
  and 10 died with no FI at autopsy
• 7 patients died, no autopsy was performed
• 1 patient died with FI at autopsy (Aspergillus.
  fum)
• Efficacy was shown in 67 out of 75 patients, 89
  

22
Proven invasive fungal infections in SOT

• A total of 56 proven infections were treated in
  50 patients
• 38 LTX, 7 KTX and 5 KPTX recipients
• 20 cholangitis (18 C. alb, 1 C. parapsilosis 1
  C. glabrata)
• 14 perotonitis (13 C. albicans 1 C. pelliculosa
  )
• 14 fungemias (13 C. albicans 1 C. glabrata)
• 4 pneumonias (2 Asp. sp, 1 C. alb glab, 1 C.
  alb.)
• 3 disseminated inf. (C. alb.)
• 1 urinary tract infection (C. alb)

23
Efficacy, proven invasive fungal infections in SOT

• Out of 50 patients with proven infections
• 14 patients died
• 10 were FI negative at autopsy
• 3 was positive for fungi at autopsy
• 1 was not autopsied
• Survival or mycotic clearance was found in 46 out
  of 50, 92 of the patients

24
Conclusion solid organ transplantation

• 10 years experience of Ambisome treatment in
  solid organ transplant recipients at one single
  center has revealed
• AmBisome treatment was safe
• AmBisome treatment was efficacious as seen as
  survival or mycotic clearance in 92 of proven
  fungal infections in SOT patients
• Efficacy in suspected FI was 89 clinical cures

25
General conclusion prophylaxis treatment in
transplantation

• Prophylaxis with AmBisome
• Efficacious in Liver transplantation
• Treatment with AmBisome
• Efficacious and safe in solid organ
  transplantation