REFRACTORY ITP

1
REFRACTORY ITP

• Persistence of thrombocytopenia after initial
  therapy, including splenectomy, with the need of
  active treatment to maintain a safe platelet
  count or to avoid bleeding symptoms

2
RESPONSE TO TREATMENT IN ITP SUMMARY OF AN IDEAL
10-YRS FOLLOW UP

• Moderate ITP no treatment remain stable 5-10
  will be reclassified as secondary 
• Severe ITP
• lt 5 primarily refractory to first line
  therapies
• 1020 stable response to corticosteroids
• 80-90 require splenectomy within 6 months
• 5 - 10 late spontaneous remission
• 65 75 stable response
• 15 20 require second line treatment (at least
  on demand)
• lt 5 spontaneous remission
• 75-85 responsive (10-15 of initial cohort)
• 10-15 unresponsive (5 of initial cohort)

3
Refractory ITP
Hemorrhagic risk of ITP lt30.000/mcL (Cohen et al,
2000) Fatal hemorrhage
-meta-analysis of 17 studies, 1.817 patients with
platelet count lt 30.000/mcL -mean follow-up
from 1.258 to 3.023 patient-year -49 cases (31
SNC, 8 others sites) (9 studies) -annual rate
from 0.0162 to 0.0389 cases per
patient-year -rate for age 0.004 cases per
patient-year for age lt 40 years
0.13 cases per patient-years for age gt 60
years
4
Refractory ITP
Hemorrhagic risk of ITP lt30.000/mcL (Cohen et al,
2000) Non-fatal hemorrhage
-meta-analysis of 17 studies, 1.817 patients with
platelet count lt 30.000/mcL -mean follow-up
from 77 to 105 patient-years -29 cases (major
episodes) (2 studies) -annual rate from 0.276 a
0.376 cases per patient-year -rate for age
0.03cases per patient-year for age lt 40 years
0.71 cases per patient-year for
age gt 60 years
5
Refractory ITPmortality risk of ITP lt30.000/mcL
(Portijelie et al, 2000)

• 4 deaths within the first 2 years follow-up (1
  for hemorrhage, 2 for infection during steroid
  therapy, 1 for post-splenectomy sepsis)
• - 20 deaths during the long term
  follow-up(median 10 years) 2 ITP- related (1
  for hemorrhage, 1 for infection) 18 ITP not
  related

6
Refractory ITP

Mortality in refractory patients   Author
Haemorrhage-related deaths
Deaths due to
infection    Shatner et al 1994
1/120-480 (0.8) 2/120-480 (1.6)  George
et al 1996 25/465 (5)
NR  Cohen
et al 2000 49/1817 (2.6)
NR  Vianelli et al 2001
1/33 (3)
0/33  Portielje et al 2001
1/12 (8.3) 1/12 (8.3)  McMillan
et al 2001 3/13 (23) 2/13
(15)    Total 80/2460 (3.2)
5/178 (2.8)  
7
Refractory ITPa challenge

• Propose a widely accepted definition of
  refractory ITP
• Prospective inception cohort study (GIMEMA
  experience) for refractory ITP patients, to
  identify the clinical outcome
• Identify high risk patients for bleeding
• Clinical trial to identify splenectomy-sparing
  therapy
• Clinical and biological prospective study to
  identify factors associated with response to
  splenectomy
• Randomized clinical trial to identify the
  treatments with the most favourable cost-benefit
  ratio, including quality of life assessment