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In utero hematopoietic stem cell transplantation: Rationale for continued work toward human...
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570 EFFECT OF A PRIOR AMNIOCENTESIS IN PATIENTS UNDERGOING LASER THERAPY FOR TWIN-TWIN TRANSFUSION SYNDROME RAMEN CHMAIT 1 , CRISTINA ROSSI 1 , RUBEN QUINTERO 1 , 1 Florida Institute for Fetal Diagnosis and Therapy, Tampa, Florida OBJECTIVE: To assess the implications of a previous therapeutic amniocen- tesis (PTA) in patients that subsequently underwent laser therapy for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: All twin pregnancies that underwent laser therapy for TTTS from January 1999 through December 2003 were studied. Patients with no PTA (PTA-) were compared to those with one or more PTA’s (PTA+) in regards to demographics, operative complications, and outcome measures including gestational age at delivery and survival of at least one neonate. Statistical significance was determined if P ! .05. RESULTS: Three hundred and forty patients underwent laser therapy for TTTS during the study period. Of these, 203 (60%) were PTA- and 137 (40%) were PTA+. The median number of amniocenteses in the PTA+ group was 1 (range 1-6), with a median total volume withdrawn of 1550cc (range 100-12000). Severity of the disease was similar between the two groups in terms of Quintero stages I/II and stages III/IV. On average, the PTA- group underwent surgery one week earlier than the PTA+ group (20.1 vs. 21.2 weeks’ gestation, P = .0001). Placental location was anterior more often in the PTA- (49%) than in the PTA+ (36%, P = .019) group, yet amnioexchange to correct blood discolored amniotic fluid was necessary less often in the PTA- (9%) than in PTA+ (20%, P = .009) group. Gestational age at delivery was greater in the PTA- than in the PTA+ patients (32.0 vs. 30.6 weeks, P = .008), with a trend towards improved survival (89% vs. 81%, P = .0543). CONCLUSION: Therapeutic amniocentesis prior to laser therapy is associated with increased operative risk, earlier gestational age at delivery, and a trend towards lower perinatal survival. Patients with TTTS who desire laser therapy should avoid undergoing prior therapeutic amniocenteses. 571 INCREASED INCIDENCE OF CARDIAC ANOMALIES IN PREGNANCIES COMPLICATED BY GASTROSCHISIS LIZA KUNZ 1 , WILLIAM GILBERT 1 , DENA TOWNER 1 , 1 University of California, Davis, Obstetrics & Gynecology, Sacramento, California OBJECTIVE: To determine the incidence of congential heart defects in infants with gastroschisis. STUDY DESIGN: California hospital discharge data from acute care civilian hospitals during the years 1992-1997 was searched for the diagnosis of gastro- schisis repair, thus identifying 621 infants. The diagnosis of congenital cardiac defect (ICD 9-CM codes 745-747) and other demographic and pregnancy outcomes were examined. RESULTS: The overall incidence of congenital cardiac defects found in this population of neonates was 11% (69/621), compared to a background rate of 6- 8/1000. There were 3 major structural anomalies: one case of Tetralogy of Fallot, one coarctation of the aorta, and one case of Ebstein’s anomaly. There were 12 right heart lesions: 10 defects in the pulmonary outflow tract, valve or artery, and 2 tricuspid valve abnormalities. There were 35 septation defects: 13 ventricular septal defects and 22 atrial septal defects. There were 35 cases of patent ductus arteriosus, of which 10 were in infants born at term. There were 16 infants with more than one lesion. 42 infants had only patent ductus arteriosus and/or atrial septal defects, possibly respresenting persistant fetal circulation rather than true defects. Excluding these cases, 25 infants remain, for an incidence rate of 4% which is still elevated over the backgroud rate. Analysis regarding maternal demographics, prenatal care, gestational age, length of stay, or requirement for major bowel surgeries were not significantly different between the infants with and without true structural defects. CONCLUSION: Contrary to conventional teaching that gastroschisis is an isolated anomaly, we found a cardiac anomaly rate significantly higher than that in the background population (4.0% vs 0.6-0.8%). Right sided lesions were present in nearly half of these infants, possibly suggesting a common etiology with development of the gastroschisis. Our data would suggest that detailed antepartum and post-natal echocardiographic evaluations are indicated in fetuses identified with gastroschisis. 572 PLACENTAL ANGIOGRAPHY OF DOUBLE SURVIVORS AND DOUBLE FETAL DEATHS AFTER LASER FOR TWIN TWIN TRANSFUSION SYNDROME (TTTS) LIESBETH LEWI 1 , MIEKE CANNIE 2 , JACQUES JANI 1 , VINCENT VANDECAVEYE 2 , STEVEN DYMARKOWSKI 3 , AGNES HUBER 4 , ROMAINE ROBYR 5 , EDUARD GRATACOS 6 , KYPROS NICOLAIDES 7 , KURT HECHER 4 , YVES VILLE 5 , JAN DEPREST 1 , 1 University Hospital Gasthuisberg, Obstetrics and Gynecology, Leuven, Belgium, 2 University Hospital Gasthuisberg Leuven, Radiology, Leuven, Belgium, 3 University Hospital Gasthuisberg, Radiology, Leuven, Belgium, 4 Universita¨ tsklinikum Hamburg- Eppendorf, Obstetrics/Gynecology, Hamburg, Germany, 5 Universite´ Paris- Ouest Poissy France, Obstetrics and Gynecology, Poissy Cedex, France, 6 Universitat Autonoma Barcelona, Barcelona, Spain, 7 King’s College Hospital, Harris Birthright Research Centre, London, United Kingdom OBJECTIVE: Placental injection study to detect residual feto-fetal anastomo- ses by inspection of the chorionic surface and Rx angiography in double survivors (2SURV) or death (2IUFD) after laser for TTTS. STUDY DESIGN: Single shot digital angiography (Philips DSI, 96 KV-224 mAs) was performed after injection of cord vessels with dyed barium (Micro- paqueÒ) as well as digital photography (Sony Cybershot 5 Mpixel) of angioarchitecture as visible on the chorionic plate. The presence of residual anastomoses visible on the chorionic surface and angiography was determined. RESULTS: 16 consecutive placentas were examined;four from 2IUFD within 1-14 days post-laser and 12 from double survivors, delivered at median GA of 34 wks (30-38). TTTS had resolved in all 2SURV; 2 had discordant Hb at birth (8/ 19 at 30wk; 12/20 g/dL at 35wk). The former had discordant Vmax MCA 2 wks post-laser, managed by one IUT. The latter had normal Vmax MCA. In all 2IUFD, residual AV-VA anastomoses were visible on the chorionic plate, on angiography being typical shared cotyledons. In 2SURV, areas of coagulation along the equator and no visible residual anastomoses could be seen on the surface, suggesting successful bichorionisation. In contrast angiography revealed atypical anastomoses in all but one. Angiographic anastomoses were either (1) intercotyledonary capillaries not visible on the chorionic surface or (2) small paired/unpaired vessels of 0.5 mm (0-1.2) visible on the chorionic surface, going from one twin and dropping unexpectedly into cotyledonary territory of the other. CONCLUSION: In 2SURV, laser bichorionises on placental inspection but not on angiography. Anastomoses visible only on angiography did not prevent resolution of TTTS, and may account for lesser degrees of feto-fetal transfusion showing need for follow-up. In 2IUFD, residual AV-VA anastomoses remained visible on the surface, suggesting surgical failure. *Sponsored by the European Commission QLG1CT2002-01632 Eurofoetus. 573 IN UTERO HEMATOPOIETIC STEM CELL TRANSPLANTATION: RATIONALE FOR CONTINUED WORK TOWARD HUMAN APPLICATION SCOTT PETERSEN 1 , MARIYA GENDELMAN 1 , RICHARD JONES 2 , ALLEN CHEN 2 , KARIN BLAKEMORE 1 , 1 Johns Hopkins University, Gynecology & Obstetrics, Baltimore, Maryland, 2 Johns Hopkins University, Oncology Center, Baltimore, Maryland OBJECTIVE: The objective of this study was to ascertain disorders for which in utero hematopoietic stem cell transplantation (IUHSCT) would be feasible based upon recent improvements in postnatal HSCT treatment protocols and disease outcomes. STUDY DESIGN: We reviewed the current literature for human diseases where application of IUHSCT may be feasible. We focused our search to create a list of diseases where low levels of initial engraftment or mixed chimerism can affect a cure. We compiled cost data from human attempts at IUHSCT from our institution and reviewed cost data for non-HSCT disease treatment from the recent literature. RESULTS: Disorders amenable to IUHSCT include the hemoglobinopathies, storage disorders, and granulocyte disorders. Of these, hemoglobinopathies appear to be the best candidates for early human trials. Using ablative preparations before postnatal HSCT, 80-85% of patients with sickle cell anemia and b-thalassemia can live disease free. Approximately 10% of these patients display mixed chimerism and not full engraftment although they remain transfusion independent despite as little as 10% donor chimerism. Mortality and morbidity have been decreased with recent less ablative and non-ablative regimens that have been found to be similarly effective. These results suggest that IUHSCT might be applicable to these diseases at a cost of $10,000. This compares to an average lifetime cost for treatment of $500,000 and $1.5 million for sickle cell anemia and b-thalassemia, respectively. CONCLUSION: Potential candidates for human application of IUHSCT include b-thalassemia, sickle cell anemia, and granulocyte disorders. As advances are made in animal models, IUHSCT may become a feasible and cost-effective treatment strategy for these diseases, and potentially others. Given the impact of these diseases on the general population, research funding should continue for advancement toward human applications. S162 SMFM Abstracts
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Transcript of In utero hematopoietic stem cell transplantation: Rationale for continued work toward human...
570 EFFECT OF A PRIOR AMNIOCENTESIS IN PATIENTS UNDERGOING LASER THERAPYFOR TWIN-TWIN TRANSFUSION SYNDROME RAMEN CHMAIT1, CRISTINA ROSSI1,RUBEN QUINTERO1, 1Florida Institute for Fetal Diagnosis and Therapy, Tampa,Florida
OBJECTIVE: To assess the implications of a previous therapeutic amniocen-tesis (PTA) in patients that subsequently underwent laser therapy for twin-twintransfusion syndrome (TTTS).
STUDY DESIGN: All twin pregnancies that underwent laser therapy for TTTSfrom January 1999 through December 2003 were studied. Patients with no PTA(PTA-) were compared to those with one or more PTA’s (PTA+) in regards todemographics, operative complications, and outcome measures includinggestational age at delivery and survival of at least one neonate. Statisticalsignificance was determined if P ! .05.
RESULTS: Three hundred and forty patients underwent laser therapy forTTTS during the study period. Of these, 203 (60%) were PTA- and 137 (40%)were PTA+. The median number of amniocenteses in the PTA+ group was 1(range 1-6), with a median total volume withdrawn of 1550cc (range 100-12000).Severity of the disease was similar between the two groups in terms of Quinterostages I/II and stages III/IV. On average, the PTA- group underwent surgery oneweek earlier than the PTA+ group (20.1 vs. 21.2 weeks’ gestation, P = .0001).Placental location was anterior more often in the PTA- (49%) than in the PTA+(36%, P = .019) group, yet amnioexchange to correct blood discolored amnioticfluid was necessary less often in the PTA- (9%) than in PTA+ (20%, P = .009)group. Gestational age at delivery was greater in the PTA- than in the PTA+patients (32.0 vs. 30.6 weeks, P = .008), with a trend towards improved survival(89% vs. 81%, P = .0543).
CONCLUSION: Therapeutic amniocentesis prior to laser therapy is associatedwith increased operative risk, earlier gestational age at delivery, and a trendtowards lower perinatal survival. Patients with TTTS who desire laser therapyshould avoid undergoing prior therapeutic amniocenteses.
571 INCREASED INCIDENCE OF CARDIAC ANOMALIES IN PREGNANCIES COMPLICATEDBY GASTROSCHISIS LIZA KUNZ1, WILLIAM GILBERT1, DENA TOWNER1, 1University ofCalifornia, Davis, Obstetrics & Gynecology, Sacramento, California
OBJECTIVE: To determine the incidence of congential heart defects in infantswith gastroschisis.
STUDY DESIGN: California hospital discharge data from acute care civilianhospitals during the years 1992-1997 was searched for the diagnosis of gastro-schisis repair, thus identifying 621 infants. The diagnosis of congenital cardiacdefect (ICD 9-CM codes 745-747) and other demographic and pregnancyoutcomes were examined.
RESULTS: The overall incidence of congenital cardiac defects found in thispopulation of neonates was 11% (69/621), compared to a background rate of 6-8/1000. There were 3 major structural anomalies: one case of Tetralogy of Fallot,one coarctation of the aorta, and one case of Ebstein’s anomaly. There were 12right heart lesions: 10 defects in the pulmonary outflow tract, valve or artery,and 2 tricuspid valve abnormalities. There were 35 septation defects: 13ventricular septal defects and 22 atrial septal defects. There were 35 cases ofpatent ductus arteriosus, of which 10 were in infants born at term. There were 16infants with more than one lesion. 42 infants had only patent ductus arteriosusand/or atrial septal defects, possibly respresenting persistant fetal circulationrather than true defects. Excluding these cases, 25 infants remain, for anincidence rate of 4% which is still elevated over the backgroud rate. Analysisregarding maternal demographics, prenatal care, gestational age, length of stay,or requirement for major bowel surgeries were not significantly different betweenthe infants with and without true structural defects.
CONCLUSION: Contrary to conventional teaching that gastroschisis is anisolated anomaly, we found a cardiac anomaly rate significantly higher than thatin the background population (4.0% vs 0.6-0.8%). Right sided lesions werepresent in nearly half of these infants, possibly suggesting a common etiologywith development of the gastroschisis. Our data would suggest that detailedantepartum and post-natal echocardiographic evaluations are indicated infetuses identified with gastroschisis.
572 PLACENTAL ANGIOGRAPHY OF DOUBLE SURVIVORS AND DOUBLE FETAL DEATHSAFTER LASER FOR TWIN TWIN TRANSFUSION SYNDROME (TTTS) LIESBETH LEWI1,MIEKE CANNIE2, JACQUES JANI1, VINCENT VANDECAVEYE2, STEVEN DYMARKOWSKI3,AGNES HUBER4, ROMAINE ROBYR5, EDUARD GRATACOS6, KYPROS NICOLAIDES7,KURT HECHER4, YVES VILLE5, JAN DEPREST1, 1University Hospital Gasthuisberg,Obstetrics and Gynecology, Leuven, Belgium, 2University HospitalGasthuisberg Leuven, Radiology, Leuven, Belgium, 3University HospitalGasthuisberg, Radiology, Leuven, Belgium, 4Universitatsklinikum Hamburg-Eppendorf, Obstetrics/Gynecology, Hamburg, Germany, 5Universite Paris-Ouest Poissy France, Obstetrics and Gynecology, Poissy Cedex, France,6Universitat Autonoma Barcelona, Barcelona, Spain, 7King’s CollegeHospital, Harris Birthright Research Centre, London, United Kingdom
OBJECTIVE: Placental injection study to detect residual feto-fetal anastomo-ses by inspection of the chorionic surface and Rx angiography in doublesurvivors (2SURV) or death (2IUFD) after laser for TTTS.
STUDY DESIGN: Single shot digital angiography (Philips DSI, 96 KV-224mAs) was performed after injection of cord vessels with dyed barium (Micro-paque�) as well as digital photography (Sony Cybershot 5 Mpixel) ofangioarchitecture as visible on the chorionic plate. The presence of residualanastomoses visible on the chorionic surface and angiography was determined.
RESULTS: 16 consecutive placentas were examined;four from 2IUFD within1-14 days post-laser and 12 from double survivors, delivered at median GA of 34wks (30-38). TTTS had resolved in all 2SURV; 2 had discordant Hb at birth (8/19 at 30wk; 12/20 g/dL at 35wk). The former had discordant Vmax MCA 2 wkspost-laser, managed by one IUT. The latter had normal Vmax MCA. In all2IUFD, residual AV-VA anastomoses were visible on the chorionic plate, onangiography being typical shared cotyledons. In 2SURV, areas of coagulationalong the equator and no visible residual anastomoses could be seen on thesurface, suggesting successful bichorionisation. In contrast angiography revealedatypical anastomoses in all but one. Angiographic anastomoses were either (1)intercotyledonary capillaries not visible on the chorionic surface or (2) smallpaired/unpaired vessels of 0.5 mm (0-1.2) visible on the chorionic surface, goingfrom one twin and dropping unexpectedly into cotyledonary territory of theother.
CONCLUSION: In 2SURV, laser bichorionises on placental inspection but noton angiography. Anastomoses visible only on angiography did not preventresolution of TTTS, and may account for lesser degrees of feto-fetal transfusionshowing need for follow-up. In 2IUFD, residual AV-VA anastomoses remainedvisible on the surface, suggesting surgical failure. *Sponsored by the EuropeanCommission QLG1CT2002-01632 Eurofoetus.
S162 SMFM Abstracts
573 IN UTERO HEMATOPOIETIC STEM CELL TRANSPLANTATION: RATIONALE FORCONTINUED WORK TOWARD HUMAN APPLICATION SCOTT PETERSEN1,MARIYA GENDELMAN1, RICHARD JONES2, ALLEN CHEN2, KARIN BLAKEMORE1, 1JohnsHopkins University, Gynecology & Obstetrics, Baltimore, Maryland, 2JohnsHopkins University, Oncology Center, Baltimore, Maryland
OBJECTIVE: The objective of this study was to ascertain disorders for whichin utero hematopoietic stem cell transplantation (IUHSCT) would be feasiblebased upon recent improvements in postnatal HSCT treatment protocols anddisease outcomes.
STUDY DESIGN: We reviewed the current literature for human diseases whereapplication of IUHSCT may be feasible. We focused our search to create a list ofdiseases where low levels of initial engraftment or mixed chimerism can affecta cure. We compiled cost data from human attempts at IUHSCT from ourinstitution and reviewed cost data for non-HSCT disease treatment from therecent literature.
RESULTS: Disorders amenable to IUHSCT include the hemoglobinopathies,storage disorders, and granulocyte disorders. Of these, hemoglobinopathiesappear to be the best candidates for early human trials. Using ablativepreparations before postnatal HSCT, 80-85% of patients with sickle cell anemiaand b-thalassemia can live disease free. Approximately 10% of these patientsdisplay mixed chimerism and not full engraftment although they remaintransfusion independent despite as little as 10% donor chimerism. Mortalityand morbidity have been decreased with recent less ablative and non-ablativeregimens that have been found to be similarly effective. These results suggest thatIUHSCT might be applicable to these diseases at a cost of $10,000. Thiscompares to an average lifetime cost for treatment of $500,000 and $1.5 millionfor sickle cell anemia and b-thalassemia, respectively.
CONCLUSION: Potential candidates for human application of IUHSCTinclude b-thalassemia, sickle cell anemia, and granulocyte disorders. As advancesare made in animal models, IUHSCT may become a feasible and cost-effectivetreatment strategy for these diseases, and potentially others. Given the impact ofthese diseases on the general population, research funding should continue foradvancement toward human applications.
