Underwent Exchange Transfusion Research Articles

Effect of Low-volume Exchange Transfusion on Neonatal Hyperbilirubinaemia: A Retrospective Cohort Study

Introduction: A double volume exchange transfusion for hyperbilirubinaemia often requires more than one pack of compatible blood to fulfil the calculated volume. This is often unavailable, necessitating exchange transfusion using less than the calculated double-volume. During practice, the authors found that many patients had a positive therapeutic response even when the exchange blood volume was reduced. Aim: To study the effect of the reduced volume of blood used for exchange transfusion in neonates with hyperbilirubinaemia. Materials and Methods: A retrospective cohort study was conducted in the Neonatal Intensive Care Unit (NICU), Malankara Orthodox Syrian Church Medical College (tertiary level), Kerala, India, between January 2015 and December 2020. Total 116 patients who underwent exchange transfusion for hyperbilirubinaemia, regardless of gestational age, were included. Pre- and postexchange details, blood chemistry and haemogram were collected from the records and analysed. The patients were grouped into group 1 (80-≤120 mL/kg) and group 2 (>120-≤160 mL/kg) based on the volume of blood used for exchange transfusion. The correlation of exchange blood volume with the percentage drop in bilirubin, rebound rise of bilirubin at six hours, duration of phototherapy, and duration of admission was studied using Pearson’s/ Spearman’s correlation. Data were statistically analysed using Independent samples t-test, Paired sample t-test, and Chi-square test to determine, if there was a significant difference between the groups. Results: Out of 116 patients, group 1 had 67 (57.78%) patients, and group 2 had 49 (42.24%) patients. The mean±Standard Deviation (SD) gestational age was 37.6±1.57 weeks, and 59 (50.86%) were males. The mean±SD postexchange bilirubin was 13.12±3.85 mg/ dL in group 1 and 10.26±2.78 mg/dL in group 2, resulting in a bilirubin reduction of 40.74±12.81% and 53.81±11.67%, respectively. The rebound bilirubin at six hours (13.15±4.32 mg/dL vs 11.23±2.30 mg/dL) made no clinical difference in the management of the patient. The median duration of phototherapy was 48 hours, and the median duration of admission was five days in both groups. Conclusion: Exchange transfusion with a lower volume of blood, followed by phototherapy, can lead to a clinically acceptable reduction in serum bilirubin. Non availability of the exact 160 mL/kg of blood for exchange is not an adequate reason to delay exchange transfusion.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia

To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20mg/dL or underwent exchange transfusion). In this prospective cohort study, infants ≥34weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34weeksof gestational age.

Clinical and laboratory effects of exchange transfusion in pediatric acute lymphoblastic leukemia with hyperleukocytosis

Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Emergency complications such as hyperleukocytosis can arise as the disease develops. Exchange transfusion is one of many cytoreductive modalities to resolve the condition.
 Objective To analyze the clinical and laboratory effects of exchange transfusion in childhood acute lymphoblastic leukemia patients with hyperleukocytosis.
 Methods This analytical retrospective cohort study with a pre- and post-test design used secondary medical record data. The obtained characteristics were the incidences of dyspnea, tachypnea, headache, intracranial bleeding, hepatomegaly, splenomegaly, lymphadenopathy, abdominal pain, fever, pallor, nausea/vomiting, and skin or mucosal bleeding; hemoglobin, white blood cell, and platelet counts; and serum potassium, sodium, calcium, phosphate, blood urea nitrogen, and creatinine levels.
 Results A total of 16 patients underwent exchange transfusion; they had significant reductions of the incidence of dyspnea, tachypnea, hepatomegaly, and pallor and significant improvement in the form of elevation of hemoglobin level and decrease in white blood cell counts (P<0.05 for all) compared to pre-treatment. The remainder of the variables were not significantly different between pre- and post-treatment, but a general decrease in all clinical manifestations except intracranial bleeding was observed.
 Conclusion Exchange transfusion has the beneficial effect of resolving hyperleukocytosis and its manifestations, although correction in laboratory outcomes that remained abnormal are still needed.

Relative anemia and perioperative stroke in children with moyamoya

ObjectivesSurgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya. Materials and MethodsIn this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery. ResultsWe analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke. ConclusionsDecreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary.

Evidence that donors with variant RH genotypes are associated with unexpected Rh antibodies.

We previously reported unexpected Rh antibodies in the plasma of patients with sickle cell disease (SCD) that demonstrated common Rh specificities in the absence of transfusion of RBCs positive for that antigen. We hypothesize that these antibodies might result from transfusion of antigen-negative donor units with variant RH genotypes. Plasma testing by tube and IgG gel, extended RBC phenotyping, and HEA and RH genotyping were by standard methods. A 6-year-old female with SCD, phenotype D + C-c + E-e + K- undergoing exchange transfusion with CEK- and Fy(a-) units, presented with anti-C in the plasma, a + DAT and warm autoantibody (WAA) in the eluate. Her RH genotype was unremarkable: RHD*D/DAU0 and RHCE*ce/ce(48C). Units (n = 10) transfused over the prior 6 months were confirmed CEK- by serology and DNA testing. Most (n = 7) were Rh-negative. A unit with variant RH, RHD*DIIIa/weak partial 4.0, RHCE*ceVS.03/ceVS.02, was transfused 5 weeks prior. Anti-C and + DAT continued to demonstrate for 25 weeks. Total hemoglobin and % Hgb S did not deviate from her established baseline. We show direct association of plasma anti-C with transfusion of a C-negative unit with variant RH encoding partial D and uncommon V/VS+ hrB - phenotype. The antibody was transient, without evidence of compromised survival of transfused RBCs. The +DAT and WAA complicated workups and selection of units, and it is uncertain whether donors of the same genotype should be avoided. Minority donors are important for CEK-matching to avoid depleting Rh-negative supplies. Consideration of patient and donor RH genotypes may avoid unexpected antibodies and improve allocation of rare donations.

Evaluation of Complications Related to Exchange Transfusion due to Hyperbilirubinaemia in Newborns with or without Comorbidities

Introduction: Exchange transfusion (ET) is the first successful treatment introduced for severe neonatal jaundice considered to be a safe procedure but not risk free. Present study aimed to determine the complications related to exchange transfusion and to compare the incidence of severe complications between healthy and ill newborns. Methods: This cross sectional study was done in Neonatal Intensive Care Unit (NICU), Dhaka Shishu Hospital and Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, over 6 months from January to June 2010, included 50 newborns who underwent exchange transfusion due to hyperbilirubinaemia. Newborns with hyperbilirubinemia alone were classified as healthy, while hyperbilirubinaemia associated with other medical problems were classified as ill. Adverse events were analyzed and compared between two groups. Results: Out of 50 patients who underwent ET, 27 were healthy had jaundice only and 23 were ill. Most of the newborns with comorbidities (87%) developed at least one complication following exchange transfusion (p<0.001). Newborns with co-morbidities developed hypoglycemia (13%), hypocalcaemia (17.4%), thrombocytopenia (26.1%), sepsis (26.1%), apnoea (4.3%) and in newborns without co-morbidities, hypoglycemia, hypocalcaemia, thrombocytopenia each was found in 7.4% cases and septicemia (14.8%). Thrombocytopenia was significantly higher in ill newborns (p = 0.039). About 9% of newborns died in ill group compared to 3.7% in healthy group (p = 0.439). Conclusions: Complications and mortality were significantly higher in newborns having hyperbilirubinemia with comorbidities. Thrombocytopenia was the most frequent complication. Majority of the hyperbilirubinemic neonates with comorbidities develop at least one complication after exchange transfusion. J Bangladesh Coll Phys Surg 2023; 41: 40-45

Presentations and outcomes among sickle cell disease patients with COVID-19 at a large southern healthcare system

ABSTRACT Objectives Compared with the general population, patients with sickle cell disease (SCD) typically have substantially reduced life expectancies. It is unclear whether SCD patients who acquire COVID-19 have higher rates of complications and mortality than the general population. We sought to elucidate COVID-19 presentation and outcomes in patients with SCD. Methods Using retrospective chart review, we evaluated demographic characteristics, presenting symptoms, chest imaging findings, blood transfusion requirements, need for mechanical ventilation or pressor support, medication administration (including remdesivir and dexamethasone), and survival among individuals with SCD hospitalized with COVID-19 from March 2020 to December 2021. Results Among 72 SCD patients, increased pain was the most common presenting symptom followed by cough, fever, and dyspnea. Thirty-seven (44%) received simple transfusion and 14 (17%) underwent exchange transfusion. Lung imaging findings suggestive of COVID-19 were observed in 27 (37%) patients; 21 (29%) patients were treated with remdesivir and 26 (35%) received dexamethasone. Three patients (4%) required mechanical ventilation and pressor support; all three died from COVID complications. Conclusions Pain is the most common presenting symptom in SCD patients with COVID-19. We observed a mortality rate higher than that among the general population among patients who required mechanical ventilation and pressor support.

Thrombocytopenia in Neonates Undergoing Exchange Transfusion of Blood for Severe Neonatal Jaundice

Objective: To determine the frequency of thrombocytopenia in neonates undergoing exchange transfusion of blood for severe neonatal jaundice. Methodology: Total 200 neonates fulfilling the selection criteria were included in the study from neonatology unit, The Madinah Teaching Hospital Faisalabad during Nov, 2020 to October 2022. An informed consent was taken from parents. Demographic information (name, age, gender, and contact) was obtained. Then all neonates underwent exchange transfusion under standard procedure. After exchange transfusion 3cc Blood sample was obtained with the help of a staff nurse by using butterfly needle and 5cc BD syringe under aseptic measures. Sample was sent to the laboratory of the hospital for platelet count. If platelet count was found below 100.000/dL, thrombocytopenia was labelled (platelet count in complete blood count is <100,000/dL assessed at the end of exchange transfusion). Results: In our study, the mean age of the patients was calculated as 15.17+4.85 days. Gender distribution reveals that 94(47%) were male and 106(53%) were females. Frequency of thrombocytopenia in neonates undergoing exchange transfusion of blood for severe neonatal jaundice was recorded in 15(7.5%) of the cases, and among them 7(46.7%) were between 1-14 days and 8(53.3%) were between 15-28 days of life, p-value=0.533, regarding gender 5(33.3%) were male and 10(66.7%) were females, p-value=0.203. Conclusion: We found that the rate of thrombocytopenia in neonates having blood exchange transfusion for severe neonatal jaundice was not significantly greater than the rate in other studies. However, our results are from a single site and need to be confirmed by additional multicenter local investigations. Keywords: Severe neonatal jaundice, exchange transfusion of blood, thrombocytopenia

Pathological jaundice in late preterm neonates admitted in a tertiary hospital, Imphal: a prospective COHORT study

Background: Approximately 85% of all term and most preterms develop clinical jaundice. Hyperbilirubinrmia is defined as a total bilirubin (TB) >95th percentile on the hour-specific Bhutani normogram. Pathological jaundice implies the onset of jaundice before 24 hours of age, rate of rise in TSB of >0.2 mg/dl/hour and jaundice persisting after 14 days in term and 21 days in late-preterms. The aim of this study was to determine the incidence, progression and the predictors of pathological jaundice among the late preterm infants admitted in Paediatrics ward of a tertiary care centre, Imphal.Methods: A hospital based prospective cohort study was carried out in paediatrics department, RIMS during a period of 2 years (September 2019 to August 2022) with approval from research ethics board. Sample size was 100 based on consecutive sampling.Results: Pathological jaundice developed among 65.0% (95% CI: 54.7-74.1%) neonates. The median duration of onset was 47.0 hours. The mean bilirubin at the time of diagnosis of jaundice was 15.5 mg/dl. Three neonates underwent exchange transfusion. Of these 3, one had pre-exchange bilirubin encephalopathy. Male gender, breast feeding, sepsis, infants blood group (B +ve), jaundice among the siblings and birth trauma (birth asphyxia/cephalhematoma) were significantly associated with the development of neonatal hyperbilirubinemia.Conclusions: Jaundice is condition that is often present and constitutes one of the major risks for neurodevelopmental issues in later life and the risk is further compounded by prematurity. Hence further studies with a larger sample size on a multicentric level could add robustness to our study thereby helping in better understanding and management of the condition.

Frequency of Indirect Hyperbilirubinemia Requiring Exchange Transfusion, Etiology and its Immediate Outcome in Term Neonates in Neonatal ICU of National Institute of Child Health, Karachi

Objectives: The present study assessed the frequency of causes of indirect hyperbilirubinemia (IH) requiring exchange transfusion and its immediate adverse events of exchange transfusion in term neonates. Methods: A prospective, observational study was undertaken at the Neonatal ICU of National Institute of Child Health, Karachi between July 2021 and December 2021. Term neonates arriving at the newborn unit of NICH with indirect hyperbilirubinemia were included in this study. All enrolled neonates were monitored for clinical, biochemical, and hematological adverse events for 7 days following exchange transfusion, and a predesigned performa was used to document observations. Results: Among 730 neonates with indirect hyperbilirubinemia, a total of 63 term neonates underwent exchange transfusion. The most common causes of hyperbilirubinemia were sepsis in 19 (30.2%) patients and ABO incompatibility in 13 (20.6%) patients. The most common adverse events noted were hypokalemia, which occurred in 10 (15.9%) and thrombocytopenia, which occurred in 10 (15.9%) cases. In six patients, sepsis developed. In total, five neonates died while four developed bilirubin encephalopathy. The total serum bilirubin and direct bilirubin among patients were significantly lowered after exchange transfusion (p<0.0001). There were no umbilical catheter-related complications. Bilirubin encephalopathy was present in 4 patients. There were five deaths, but not due to the procedure. Practical implication Conclusion: We highlighted the main causes of indirect hyperbilirubinemia as sepsis and ABO incompatibility in our setting. Furthermore, we also identified the immediate and short-term outcomes of exchange transfusion with a mortality rate of 7.9%. The overall outcome was favorable after the exchange transfusion. Keywords: Hyperbilirubinemia, kernicterus, exchange transfusion, indirect bilirubin, neonates , jaundice

İndirekt Hiperbilirubinemide Exchange Transfüzyon Uygulanması: Tek Merkez Deneyimi

Objective: Hyperbilirubinemia is a common clinical condition in newborn infants, and bilirubin encephalopathy remains an important health problem today. Decreased bilirubin anxiety and inadequate etiological evaluations lead to serious problems such as kernicterus. In this study, the development of bilirubin encephalopathy and its etiological causes were evaluated in patients who received exchange transfusion due to indirect hyperbilirubinemia for a period of one year. Methods: Newborns admitted to the Neonatology clinic between September 2020 and August 2021 due to indirect hyperbilirubinemia and undergoing exchange transfusion were analyzed retrospectively. Demographic data, laboratory parameters, and incidence of complications related to exchange transfusion were investigated. Results: A total of 62 infants, 61.3%(38) boys and 38.7%(24) girls, were included in the study. 53.2%(33) of the patients were delivered by cesarean section. Mean gestational age was 38(36-41) weeks and mean birth weight was 3063±478 grams. The median age at presentation was found to be 5 (1-22) days. In the etiological evaluation of the cases, 27.4%(44) Rh incompatibility, 50%(31) ABO incompatibility, 46.8%(29) Subgroup incompatibility were observed. More than one discrepancy was detected in 33.8%(21) of the patients. Glucose 6 phosphate dehydrogenase enzyme deficiency was detected in 21% (13) of the cases. No etiological cause was found in 4.8%(3) of the patients. Conclusion: Indirect hyperbilirubinemia and related bilirubin encephalopathy still remain a serious problem and therefore exchange transfusion may be required. In order to reduce serious morbidity and even mortality due to indirect hyperbilirubinemia, bilirubin monitoring should be done closely and risky babies should be determined in advance with etiological evaluations.

Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion.

Severe neonatal hyperbilirubinemia can cause neurological disability or mortality if not effectively managed. Exchange transfusion (ET) is an efficient treatment to prevent bilirubin neurotoxicity. The purpose of this study was to evaluate outcomes in severe neonatal hyperbilirubinemia with ET and to identify the potential risk factors for poor outcomes. Newborns of ≥28 weeks of gestational age with severe hyperbilirubinemia who underwent ET from January 2015 to August 2019 were included. Demographic data were recorded and analyzed according to follow-up outcomes at 12 months of corrected age. Poor outcomes were defined as death due to bilirubin encephalopathy or survival with at least one of the following complications: cerebral palsy, psychomotor retardation (psychomotor developmental index < 70), mental retardation (mental developmental index < 70), or hearing impairment. A total of 524 infants were eligible for recruitment to the study, and 62 infants were lost to follow-up. The outcome data from 462 infants were used for grouping analysis, of which 398 cases (86.1%) had normal outcomes and 64 cases (13.9%) suffered poor outcomes. Bivariate logistic regression analysis showed that peak total serum bilirubin (TSB) (odds ratio [OR] = 1.011, 95% confidence interval [CI] = 1.008-1.015, p = 0.000) and sepsis (OR = 4.352, 95% CI = 2.013-9.409, p < 0.001) were associated with poor outcomes of hyperbilirubinemia. Receiver operator characteristic curve analysis showed that peak TSB ≥452.9 µmol/L could predict poor outcomes of severe hyperbilirubinemia. Peak TSB and sepsis were associated with poor outcomes in infants with severe hyperbilirubinemia, and peak TSB ≥452.9 µmol/L could predict poor outcomes.

High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates

BackgroundAlthough it is known that unbound bilirubin can enter the brain, there is little evidence of its association with the development of acute bilirubin encephalopathy. Here, we investigated this potential relationship in neonates who had undergone exchange transfusion.MethodsData from 46 newborns who underwent exchange transfusion between 2016 and 1-1 to 2018-12-31 at the First People’s Hospital of Changde City in China were analyzed. The unbound bilirubin level was taken as the independent variable and the development of the acute bilirubin encephalopathy as the dependent variable. The covariates were age, birth weight, sex, red blood cell count, blood glucose, hemolytic disease, and whether the infant had received phototherapy.ResultsThe mean age and gestational age of the neonates were 146.5 ± 86.9 h and 38.6 ± 1.3 weeks [38.7(34.6–41.1) weeks] old, respectively; 52.17% were male. Binary logistic regression analysis after adjustment for covariates showed a positive association between the levels of unbound bilirubin and the development of acute bilirubin encephalopathy (odds ratio = 1.41, 95% confidence intervals 1.05–1.91, P = < 0.05).ConclusionThere is a significant association between unbound bilirubin levels and the development of acute bilirubin encephalopathy in neonates. Further investigations are required to explore the mechanisms.

Frequency of Hypocalcemia with Exchange Transfusion in Neonatal Jaundice

Aim: To determine the frequency of hypocalcemia with exchange transfusion in neonatal jaundice. Study design: Descriptive cross-sectional study Place and duration of study: Departments of Pediatrics and Pathology, Naseer Teaching Hospital Peshawar from 1stJanuary 2018 to 31st December 2018. Methodology: One hundred and sixty twopatients of jaundiced neonates having total serum bilirubin &gt;20mg/dl, both gender and patients having age up to 14 days were included. Patients fulfilling the selection criteria had undergone exchange transfusion. Hypocalcaemia was evaluated and considered positive if calcium serum level is &lt;8 mg/dl or &lt;2 mmol/L. Results: 50% of neonates were between 1-5 days, 45% of neonates were between 5-10 days, and 3% of neonates were in age 10-14 days. One hundred and ten (68%) of neonates were males and 52 (32%) of neonates were females. 30% neonates had hypocalcemia while 70% were without hypocalcemia. Conclusion: The incidence of hypocalcemia was found to be 30% with exchange transfusion in neonatal jaundice. Keywords: Hypocalcemia, Exchange transfusion, Neonatal jaundice

Is it necessary to give calcium infusion during the exchange transfusion in newborns?

ObjectivesWe aimed to evaluate total serum calcium (TSC) and ionized serum calcium (ISC) levels and their effects on clinical outcomes in neonates underwent exchange transfusion (ET). MethodIn this study, the data of newborn infants who underwent ET due to hyperbilirubinemia in a third level neonatal intensive care unit (NICU) were retrospectively analyzed. The patients were monitored by electrocardiogram during ET. Cardiac and respiratory rates, peripheral oxygen saturation, blood pressure values ​​and clinical findings as convulsion, tremor, hypertonia, laryngospasm, cyanosis and apnea were recorded in ET observation forms. The infants with no symptoms of hypocalcemia during the procedure were not routinely given IV calcium gluconate. TSC and ISC measured at the beginning, at the end and 24 h after the end of ET were evaluated retrospectively. ResultsData of 36 newborn patients were evaluated. Median gestational age was 39 (35−40) weeks, mean birthweight was 2840 ± 841 (mean ± SD) grams. During the ET, desaturation was observed in five patients(13.9 %), sinus bradycardia in six(16.7 %), tachypnea in two(5.5 %), sinus tachycardia in one(2.8 %), and rare ventricular extrasystoles in one(2.8 %). Hypocalcaemia was not detected in any of the patients at the beginning of ET. Hypocalcemia was observed in two cases (5.5 %) at the end of ET. There was no statistically significant difference between the TSC and ISC levels at the beginning of ET, at the end and at the end of 24 h. ConclusionAs a result, routine intravenous (IV) calcium administration seems to be unnecessary provided that vital signs and neurological status are closely monitored during ET.

Comparable Outcome of CD3+-/CD19+ Depleted Haploidentical with Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Advanced Stage Sickle Cell Disease: Result of a Pilot Study

IntroductionSickle cell disease (SCD) is an inherited disorder with an estimate of 300.000 affected newborns per year worldwide. Despite significant improvements in preventive measures, supportive care and conventional therapy, substantial morbidity and mortality with a reduced life expectancy persists. Allogeneic hematopoietic stem cell transplantation (HSCT) with a matched sibling donor (MSD) is currently the curative standard of care for SCD patients (pts). But MSD and unrelated matched donor availability is <20% and graft- versus-host disease (GvHD) remains to be associated with significant morbidity and mortality with T cell repleted grafts and standard GvHD prophylaxis, which is unacceptable, particularly in pts with non-malignant diseases. A T cell depleted haploidentical HSCT (T-haplo-SCT) expands donor availability while exhibiting low GvHD rates. In our single center pilot study, we compared T-haplo-SCT with a MSD HSCT in pts with advanced stage SCD, using almost identical transplant conditions except donor source and GvHD prophylaxis.Methods17 pts were transplanted for advanced stage SCD-related complications. Five SCD pts received bone marrow (BM) from a MSD and 12 peripheral blood stem cells (PBSC) from a haploidentical donor. The conditioning regimen for both groups consisted of thiotepa (2x5mg/kg), fludarabine (4x40mg/m2), treosulfan (3x14g/m2) and anti-thymocyte globulin (ATG, Neovii, 3x15mg/kg), given on day -9 to -7 for T-haplo-SCT and on days -3 to -1 for MSD. In addition, Cyclosporine A (CSA) or Tacrolimus and MMF was applied for GvHD prophylaxis. All pts underwent exchange transfusions prior to conditioning and means of fertility preservation. The MSD pts included four females and one male, median age 22 years (range 9 to 25 years). Three suffered from homozygous SCD, two from HbS/ß-thalassemia. The BM graft consisted of a median of 2,2 x 106 CD34+ cells/kg bodyweight, with a A/S in three and a A/A genotype in two donors. In T-haplo-SCT, five were females and seven were males. Median age was 18 yrs (range 3 to 28 yrs). Nine had homozygous SCD, three HbS/ß-thalassemia. The PB grafts consisted of a median of 12,2 x 106 CD34+ cells, 11,2 x 103 CD3+ and 23,3 x 103 CD19+ cells/kg. Haploidentical donors were fully haplotype mismatched relatives (1 mother, 8 fathers, 1 cousin, 1 sister and one step sister). Donor genotype was Hb A/A in one and Hb A/S in all others.ResultsThe median follow-up was 21 months in the MSD group and 26 months in T-haplo-SCT group. The median hospitalization was 38 days for both. The median time to engraftment was faster in T-haplo-SCT versus MSD: 16 versus 23 days for leukocytes, 18 versus 23 days for granulocytes and 11 versus 21 days for thrombocytes. The median T (>500/µl) and B cell recovery (>100/µl) in T-haplo-SCT versus MSD was 115 versus 103 days and 85 versus 140 days, respectively.Two pts in the T-haplo-SCT group developed a stable mixed PB chimerism with no SCD-related complications off immunosuppression. Lineage specific chimerism analyses of red cell precursors (CD235a, glycophorine A) in the BM of these pts showed a complete red cell chimerism. The median HbS level off immunosuppression was comparable in both groups (37-38%). In all 17 pts, the conditioning regimen was well tolerated. Mild veno-occlusive disease (VOD/SOS) was diagnosed in 1 MSD patient and a transient thromboembolic event in one T-haplo-SCT patient. One patient developed a life threatening capillary leak syndrome during ATG treatment and subsequent PRES and was rescued by a switch to everolimus MMF prophylaxis. One patient from the T-haplo-SCT succumbed to a CMV pneumonitis combined with rotavirus gastroenteritis. None of our pts developed a grade III-IV acute GvHD. Five T-haplo-SCT and one MSD patient developed steroid responsive grade I-II acute GvHD. One of five MSD and three of twelve T-haplo-SCT pts developed mild to moderate steroid responsive chronic GvHD, which resolved in the meantime. CMV and EBV reactivations were observed but could be treated with standard of care except one patient mentioned above. One patient after T-haplo-SCT developed BK virus nephritis. All pts are stably engrafted off immunosuppression and free of SCD-related complications.ConclusionsIn our experience T-haplo-SCT with CD3+/CD19+ depleted PBSC is safe and efficient with a very low incidence of GvHD and is at least comparable to MSD HSCT, even for advanced stage SCD pts. DisclosuresCorbacioglu:Jazz Pharmaceuticals: Consultancy, Honoraria.

To study the outcome of exchange transfusion in severe neonatal sepsis in neonates admitted in NICU at Dr. Bhim Rao Ambedkar memorial hospital, Raipur, Chhattisgarh, India

Background: Sepsis is one of the most common causes of neonatal mortality and morbidity.Immaturity of the immune system, newborn infants are highly susceptible to systemic infection.Blood exchange transfusion in severe neonatal sepsis remove bacteria, bacterial toxins, andcirculating pro-inflammatory cytokines, improve perfusion and tissue oxygenation, correct theplasma coagulation system and enhance immunological defence mechanisms. Material andmethods: This is a hospital-based, time-bound, analytical observational study conducted fromJanuary 2019 to December 2019 in the NICU of Dr. B.R.A.M. Hospital &amp; Pt. J. N. M. Medical College,Raipur, Chhattisgarh, India. The data was collected in pre-designed proforma, entered in MicrosoftExcel and analysis was done using SSPS v 22.0. Result: About 42 neonates were diagnosed withsevere neonatal severe. Of which 23 (54.76%) were preterm, 42.24% were term neonates.Maximum 22 (52.38%) were VLBW, 4.76% were LBW and 19.05% were with normal birth weight. Inthe study two-third of 28 (66.67%) were outborn and one third were inborn. In the present studymajority of 30 (71.43%) had EOS and 12 (28.57%) had LOS. In our study out of 42 study subjects24 (57.14%) died and 18 (42.86%) were discharged after blood exchange transfusion. Of those whodied 15 (62.5%) were preterm and of those discharged 10 (55.6%) were term neonates (p=0.349).Outborn neonates more died as compare to inborn though this was also not significant (p=0.133).Conclusion: significant reduction of mortality in patients who underwent exchange transfusion,together with the no adverse effects observed, suggest that this procedure should be considered forthe treatment of neonates with severe sepsis.

Corticosteroids for management of Rh-isoimmunization, extended study in a tertiary referral centre.

Background: RhD isoimmunization is a life threatening condition for affected fetuses. It is currently treated only by intrauterine transfusion of packed red blood cells. This procedure required special skill and has potential complications.Aim : The aim of the present study was to evaluate the role of corticosteroids in prevention of fetal anemia due to RhD isoimmunization.Material and Methods: The study was conducted on 15 pregnant patients with RH isoimmunization in Shatby Maternity University Hospital, Alexandria, Egypt, during the period from July 30th 2016 to July 30th 2019. Recruited women received 40 mg oral prednisolone starting from 10th week of gestation. Follow up of Anti-Rh antibodies titer and-from 18 weeks gestation- middle cerebral artery peak systolic velocity (MSA-PSV) was done every 2 weeks. Patients were delivered at 34 weeks gestation by elective caesarean section after receiving 4 doses of dexamethasone to enhance fetal lung maturity.Results: 12 patients continued the trial. Significant reduction was achieved in anti-Rh antibodies titer. Reduction in MSA-PSV was achieved and maintained below 1.5 MOM. Gestational age at delivery ranged from30.3-34 weeks (33.18±1.2 weeks). Fetal eight at delivery ranged from 1550-2270 grams (1978.5±232.5 gm). 9 newborns required NICU admission, only 2 newborns underwent exchange transfusion therapy.Conclusion: In Rh iso-immunization, oral prednisolone proved to have a good rule in preventing fetal anemia and introducing its use should be considered. More studies with bigger sample size are needed to confirm its efficacy

Bentall Procedure for an Adolescent with Sickle Cell Disease, Hodgkin’s Lymphoma, and old Cerebrovascular Accident

Cardiopulmonary bypass (CPB) in patients with sickle cell anemia can trigger lethal vaso-occlusive crises, especially in cases of hypoxia, hypothermia, acidosis, or low-flow states. We described a patient with sickle cell anemia who had bicuspid aortic valve stenosis and aneurysmal dilatation of the ascending aorta complicated with infective endocarditis. The patient had a history of stroke. During routine workup, Hodgkin’s Lymphoma was diagnosed. The patient underwent exchange transfusion preoperatively and immediately before the initiation of CPB. We performed a Bentall procedure, and the patient was discharged in a stable condition. Sickle Cell Disease can be very challenging during CPB, and special precautions are required to prevent vaso-occlusive crises.

Exposure to a mycovirus containing Aspergillus Flavus reproduces acute lymphoblastic leukemia cell surface and genetic markers in cells from patients in remission and not controls

The etiology of acute lymphoblastic leukemia (ALL) remains unknown. A recent “two-hit” model for the occurrence of precursor B cell acute lymphoblastic leukemia propose that this disease arises through a two-step process, including predisposing genetic mutation and exposure to infections. While several genetic mutations are proposed, no infection category has been suggested. We have isolated a certain Aspergillus Flavus from residence of an ALL patient. This organism contains mycovirus and does not produce aflatoxin. The supernatant of culture of this mycovirus containing Aspergillus Flavus (SAF) was tested on the PBMCs of ALL patients in remission and controls. Cell surface phenotypes and genetic markers were examined. The effects of its combination with Epstein-Barr virus (EBV) was also investigated. For the SAF, positive and negative controls were aflatoxin and culture of Mycocladus corymbifer, respectively. Controls for ALL were sickle cell patients undergoing exchange transfusion. Incubation of the PMBCs from ALL patients in remission, or controls, with SAF resulted in re-development of ALL cell surface phenotypes and genetic markers in ALL patients in remission and not controls. These differentiating effects were not seen with aflatoxin or culture of Mycocladus Corymbifer. Addition of EBV did not alter effects of SAF. Currently, there are no techniques to discriminately reproduce characteristic leukemic genetic markers and cell surface phenotypes in cells from ALL patients in remission and not controls. These studies may provide a test for recognition of ALL patients in remission and new prospects for the investigation of leukemogenesis.