- Email: [email protected]
Have changes in UNOS status system improved allocation in pediatric heart recipients?
S64
Abstracts
The Journal of Heart and Lung Transplantation February 2005
K. Kanter,2 M. Kichuk-Chrisant,2 S. Mital,2 E. Pahl,2 1Cardiology, Hospital for Sick Children/University of Toronto, Toronto, ON, Canada; 2USA Centre; 3UK Centre, United Kingdom; 4Canadian Centre, Canada We previously reported results of ABO-incompatible (ABO-I) heart transplantation (Tx) in 10 infants (NEJM 2001;344:793). There are now 48 known cases worldwide allowing collection of multi-centre data on outcomes of ABO-I Tx. Methods: Clinical data on known cases of ABO-I infant Tx were summarized. Results: The experience with infant ABO-I Tx now includes 48 Txs in 47 patients (pts) (20 cases at our institution, 15 in USA, 10 in UK, 2 in Edmonton, 1 in Uruguay (data not included)). Age at Tx was 4hr-2.5yr (median 117d). Donor/recipient blood groups: AB/O⫽5; A/O⫽20; B/O⫽13; B/A⫽4; AB/A⫽3; A/B⫽2. This strategy was used in pre-emptively in 40 cases, only urgently in 7 cases, accidentally in one; 10 cases were Tx’d from ECMO. 13 pts had anti-donor Ab prior to Tx (titres ⬎ 1:4), including 8 ECMO pts and 3 pts aged ⬎8mo. Plasma exchange was used for antibody removal. Pts received standard immunosuppression based on individual institutional protocols. There were 8 deaths and 3 reTxs; none could be attributed to ABO-incompatibility. Mean follow-up of 37 survivors with ABO-I grafts was 36 mos (14d -13.8 yr). There was no hyperacute rejection. One 9 mo old pt developed anti-donor Ab post-Tx and delayed mild Ab-mediated rejection, successfully treated with rituximab. Antibody development otherwise was similar to our original series with a persistent, selective deficiency in anti-donor antibody. Conclusions: Consistency of the clinical and laboratory data support our contention that ABO-I heart Tx is safe in young infants. The scientific principles demonstrated in the original cohort have been observed in all cases, particularly that hyperacute rejection will not occur in the absence of anti-donor antibody. The upper age range for this strategy remains to be determined, and caution must be advised in older infants. 68 SHOULD STATUS II PATIENTS BE REMOVED FROM THE PEDIATRIC HEART TRANSPLANT WAITING LIST: A MULTIINSTITUTIONAL STUDY J.K. Kirklin,1 D.C. Naftel,1 F.B. Pearce,1 C. White-Williams,1 R.L. Caldwell,2 H. Bartlett,3 P. Rusconi,4 B.V. Robinson,5 1Univ of Alabama at Birmingham, Birmingham, AL; 2Indiana Univ Medical Center, Indianapolis, IN; 3Univ of Iowa Hospitals and Clinics, Iowa City, IA; 4Univ of Miami, Miami, FL; 5Univ of North Carolina, Chapel Hill, NC Background: The survival benefit of cardiac transplantation (CTx) among status 2 (stable outpatient) adult recipients has been questioned, but few studies have addressed this issue in pediatric patients (pts). This study examined the hypothesis that “status 2 pediatric recipients have a survival benefit with CTx”. Methods: Between 1993 and 2003, 2375 pts were listed for CTx at 24 institutions, of which 614 (26%) were status 2. By mutivariable competing outcomes hazard function analysis, death after listing and post-transplant survival were analyzed. Results: A single-phase hazard function described the risk of death after listing, with 20% actual mortality within 2 months after status 1 listing. The “natural history” of status 2 listed pts was estimated by the risk of death while waiting and risk of deterioration to status 1 at CTx (weighted by the probability of death at 3 mo after status 1 listing). At 4 months after CTx, the survival with CTx exceeded the predicted “Natural Hx” survival in all diagnostic categories out to 4 yrs of follow-up. Conclusion: 1) Pediatric pts currently listed as Status 2 have a survival benefit with transplant out to at least 4 yrs. 2) A pediatric
allocation system restricted to status 1 pts could only be justified if the vast majority of such pts could be transplanted within 1–2 months. 69 HAVE CHANGES IN UNOS STATUS SYSTEM IMPROVED ALLOCATION IN PEDIATRIC HEART RECIPIENTS? L.J. Addonizio,1 S.D. Zangwill,2 D.N. Rosenthal,3 D.C. Naftel,4 R. Korsin,1 D.T. Hsu,1 J.K. Kirklin,4 Pediatric Heart Transplant Study Group, 1Columbia University, New York, NY; 2University of Wisconsin, Milwaukee, WI; 3Stanford University, Palo Alto, CA; 4 University of Alabama, Birmingham, AL In 1999, UNOS created Status 1A and 1B and began allocating blood type O donors to O then B recipients (pts) and adolescent donors to pts ⬍ 18 years. Data from a prospective multi-institutional pediatric cohort of 2374 pts listed, 1620 transplanted (tx) at 24 institutions was used to examine the effects of these changes on time to tx and survival pre- and post-tx. Two eras were compared: early (1993–98, n⫽1247) and recent (1999 – 03, n⫽1128). In the early era, 72% of listed pts were status 1 vs. 60% 1A and 15% 1B more recently; status 2 listings were 28% vs. 25% by era. Six-month actual mortality pre-tx was 25% in status 1 pts (early), 18% in status 1A and 7% in status 1B pts (recent); in status 2 pts, mortality was 6% early and 2% recent. Tx frequency was not different between early and recent eras (68% vs. 66%). Overall mean time to tx was unchanged between eras (2.1 vs. 2.3 mo., p⫽.2); time to tx was no different in Type O or ages 5–18 years (see Table). Post-tx survival was higher in the recent era, but was not different among pre-tx status groups. Overall 1-year survival after listing was significantly higher in the recent era, 79% vs. 69% in the early era, p⬍ .01, with a survival in status 1A and 1B pts of 76% vs. 63% in status 1 pts, p⬍ .01. In summary, allocating O donors to O pts did not result in a shorter time to tx. The current UNOS system appropriately allocates donors to pediatric patients with a low wait-list mortality in status 1B and 2 pts. Overall survival in children listed for tx is improved in the more recent era, reflecting both lower mortality while waiting and improved post-tx management.
Mean Wait Time (mo.) by Era, Status, Blood Type Age (yrs)
Early Era Type O
Status 1 Type A
Type B
Recent Era Type O
Status 1A/1B Type A
Type B
0–1 1–5 5–13 13–18
1.8 .9 3.8 3.0
1.2 .6 2.7 1.7
1.1 .8 2.7 1.5
2.1/5.0 3.2/5.0 1.6/6.2 2.7/3.3
1.2/2.7 1.1/1.2 1.5/1.9 1.2/2.8
1.3/1.2 1.2/2.6 1.7/8.0 2.1/2.2
Abstracts
The Journal of Heart and Lung Transplantation February 2005
K. Kanter,2 M. Kichuk-Chrisant,2 S. Mital,2 E. Pahl,2 1Cardiology, Hospital for Sick Children/University of Toronto, Toronto, ON, Canada; 2USA Centre; 3UK Centre, United Kingdom; 4Canadian Centre, Canada We previously reported results of ABO-incompatible (ABO-I) heart transplantation (Tx) in 10 infants (NEJM 2001;344:793). There are now 48 known cases worldwide allowing collection of multi-centre data on outcomes of ABO-I Tx. Methods: Clinical data on known cases of ABO-I infant Tx were summarized. Results: The experience with infant ABO-I Tx now includes 48 Txs in 47 patients (pts) (20 cases at our institution, 15 in USA, 10 in UK, 2 in Edmonton, 1 in Uruguay (data not included)). Age at Tx was 4hr-2.5yr (median 117d). Donor/recipient blood groups: AB/O⫽5; A/O⫽20; B/O⫽13; B/A⫽4; AB/A⫽3; A/B⫽2. This strategy was used in pre-emptively in 40 cases, only urgently in 7 cases, accidentally in one; 10 cases were Tx’d from ECMO. 13 pts had anti-donor Ab prior to Tx (titres ⬎ 1:4), including 8 ECMO pts and 3 pts aged ⬎8mo. Plasma exchange was used for antibody removal. Pts received standard immunosuppression based on individual institutional protocols. There were 8 deaths and 3 reTxs; none could be attributed to ABO-incompatibility. Mean follow-up of 37 survivors with ABO-I grafts was 36 mos (14d -13.8 yr). There was no hyperacute rejection. One 9 mo old pt developed anti-donor Ab post-Tx and delayed mild Ab-mediated rejection, successfully treated with rituximab. Antibody development otherwise was similar to our original series with a persistent, selective deficiency in anti-donor antibody. Conclusions: Consistency of the clinical and laboratory data support our contention that ABO-I heart Tx is safe in young infants. The scientific principles demonstrated in the original cohort have been observed in all cases, particularly that hyperacute rejection will not occur in the absence of anti-donor antibody. The upper age range for this strategy remains to be determined, and caution must be advised in older infants. 68 SHOULD STATUS II PATIENTS BE REMOVED FROM THE PEDIATRIC HEART TRANSPLANT WAITING LIST: A MULTIINSTITUTIONAL STUDY J.K. Kirklin,1 D.C. Naftel,1 F.B. Pearce,1 C. White-Williams,1 R.L. Caldwell,2 H. Bartlett,3 P. Rusconi,4 B.V. Robinson,5 1Univ of Alabama at Birmingham, Birmingham, AL; 2Indiana Univ Medical Center, Indianapolis, IN; 3Univ of Iowa Hospitals and Clinics, Iowa City, IA; 4Univ of Miami, Miami, FL; 5Univ of North Carolina, Chapel Hill, NC Background: The survival benefit of cardiac transplantation (CTx) among status 2 (stable outpatient) adult recipients has been questioned, but few studies have addressed this issue in pediatric patients (pts). This study examined the hypothesis that “status 2 pediatric recipients have a survival benefit with CTx”. Methods: Between 1993 and 2003, 2375 pts were listed for CTx at 24 institutions, of which 614 (26%) were status 2. By mutivariable competing outcomes hazard function analysis, death after listing and post-transplant survival were analyzed. Results: A single-phase hazard function described the risk of death after listing, with 20% actual mortality within 2 months after status 1 listing. The “natural history” of status 2 listed pts was estimated by the risk of death while waiting and risk of deterioration to status 1 at CTx (weighted by the probability of death at 3 mo after status 1 listing). At 4 months after CTx, the survival with CTx exceeded the predicted “Natural Hx” survival in all diagnostic categories out to 4 yrs of follow-up. Conclusion: 1) Pediatric pts currently listed as Status 2 have a survival benefit with transplant out to at least 4 yrs. 2) A pediatric
allocation system restricted to status 1 pts could only be justified if the vast majority of such pts could be transplanted within 1–2 months. 69 HAVE CHANGES IN UNOS STATUS SYSTEM IMPROVED ALLOCATION IN PEDIATRIC HEART RECIPIENTS? L.J. Addonizio,1 S.D. Zangwill,2 D.N. Rosenthal,3 D.C. Naftel,4 R. Korsin,1 D.T. Hsu,1 J.K. Kirklin,4 Pediatric Heart Transplant Study Group, 1Columbia University, New York, NY; 2University of Wisconsin, Milwaukee, WI; 3Stanford University, Palo Alto, CA; 4 University of Alabama, Birmingham, AL In 1999, UNOS created Status 1A and 1B and began allocating blood type O donors to O then B recipients (pts) and adolescent donors to pts ⬍ 18 years. Data from a prospective multi-institutional pediatric cohort of 2374 pts listed, 1620 transplanted (tx) at 24 institutions was used to examine the effects of these changes on time to tx and survival pre- and post-tx. Two eras were compared: early (1993–98, n⫽1247) and recent (1999 – 03, n⫽1128). In the early era, 72% of listed pts were status 1 vs. 60% 1A and 15% 1B more recently; status 2 listings were 28% vs. 25% by era. Six-month actual mortality pre-tx was 25% in status 1 pts (early), 18% in status 1A and 7% in status 1B pts (recent); in status 2 pts, mortality was 6% early and 2% recent. Tx frequency was not different between early and recent eras (68% vs. 66%). Overall mean time to tx was unchanged between eras (2.1 vs. 2.3 mo., p⫽.2); time to tx was no different in Type O or ages 5–18 years (see Table). Post-tx survival was higher in the recent era, but was not different among pre-tx status groups. Overall 1-year survival after listing was significantly higher in the recent era, 79% vs. 69% in the early era, p⬍ .01, with a survival in status 1A and 1B pts of 76% vs. 63% in status 1 pts, p⬍ .01. In summary, allocating O donors to O pts did not result in a shorter time to tx. The current UNOS system appropriately allocates donors to pediatric patients with a low wait-list mortality in status 1B and 2 pts. Overall survival in children listed for tx is improved in the more recent era, reflecting both lower mortality while waiting and improved post-tx management.
Mean Wait Time (mo.) by Era, Status, Blood Type Age (yrs)
Early Era Type O
Status 1 Type A
Type B
Recent Era Type O
Status 1A/1B Type A
Type B
0–1 1–5 5–13 13–18
1.8 .9 3.8 3.0
1.2 .6 2.7 1.7
1.1 .8 2.7 1.5
2.1/5.0 3.2/5.0 1.6/6.2 2.7/3.3
1.2/2.7 1.1/1.2 1.5/1.9 1.2/2.8
1.3/1.2 1.2/2.6 1.7/8.0 2.1/2.2