Authors' Response – Pulmonary function abnormalities in Nigerian children with sickle cell anemia: Prevalence, pattern, and predictive factors

Abstract Introduction: Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Children with SCA are at high risk for ischemic stroke and transient ischemic attacks, secondary to intracranial arteriopathy involving carotid and cerebral arteries. Children with Black African variant SCA are prone to invasive infections caused by S. pneumonia, H. influenzae and Plasmodium falciparum (in malarias areas). In Africa, malaria contributes substantially to the early mortality of patients with SCA. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of Nigerian children affected by SCA. Patients and Methods: This study included 36 consecutive SCA patients who underwent bone marrow transplantation from human leukocyte antigen (HLA)-identical sibling donors between 2010 and 2015 following a myeloablative-conditioning regimen. Patients received fludarabine (30 mg/m2/day) for 5 days and a conditioning regimen including targeted intravenous busulfan (14 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose). Blood samples were collected in different Nigerian Hospitals and shipped to the Laboratory of the IME Foundation in Italy where were processed for DNA preparation on a fully automated system (Maxwell, Promega, Madison, WI). Low resolution HLA-A, -B, -C, -DRB1 and -DQB1 typing was performed using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique (LABType - One Lambda, Canoga Park, CA). Results: The median patient age was 10 years (range 2-17 years). Before transplantation, seventeen patients had recurrent, painful, vaso-occlusive crisis; twelve patients had recurrent painful crisis in association with acute chest syndrome; three patients experienced ischemic stroke and recurrent vaso-occlusive crisis; two patients experienced ischemic stroke; one patient exhibited leucocytosis; and one patient exhibited priapism. Of the 36 patients, 33 survived without sickle cell disease, with Lansky/Karnofsky scores of 100, following a myeloablative-conditioning regimen. The probabilities of survival, SCA-free survival, and transplant-related mortality after transplant were 92%, 92%, and 8%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Within the frame of the HSCT program for the treatment of SCA, a total of 124 Nigerian families with 2 to 11 children (average 2.5) were typed for five HLA loci (A, B, C, DRB1 and DQB1) and the phased genotypes were unambiguously determined. Thirty-six percent of the patients had at his disposal within the family a HLA compatible sibling. Conclusion: The protocols used for the preparation to the transplant in thalassemia are very effective also in the other severe hemoglobinopathy as in the sickle cell anemia with more than 90% disease free survival. If a SCA patient has a HLA identical family member, the allogeneic cellular gene therapy through the transplantation of the hematopoietic stem cells should be performed as soon as possible, before the disease progresses through a treatment-related irreversible organ damage. Disclosures No relevant conflicts of interest to declare.

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Pulmonary Function in Children with Sickle Cell Anemia Following Treatment with Hydroxyurea.

Blood ◽

10.1182/blood.v112.11.1435.1435 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1435-1435 ◽

Cited By ~ 1

Author(s):

Elizabeth Record ◽

Tamara New ◽

Randall Brown ◽

LeRoy Graham ◽

R. Clark Brown

Keyword(s):

Pulmonary Function ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Pulmonary Function Tests ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

P Value ◽

Chronic Injury ◽

History Of ◽

Abnormal Pulmonary Function

Abstract Background: Pulmonary function is particularly susceptible to acute and chronic injury occurring in patients with sickle cell anemia (SCA). Acute Chest Syndrome (ACS), a common and potentially fatal complication of SCA, can be the cause or the consequence of abnormal pulmonary function (Siddiqui & Ahmed, 2003). Use of hydroxyurea therapy (HU) is increasing for children with recurrent pulmonary complications, following the findings that HU reduces risk of ACS in adults (Charache et al, 1995). How HU may improve pulmonary function in children with SCA is still ill-defined. The purpose of this study was to assess the change observed on serial pulmonary function tests (PFT) for children prescribed HU for abnormal pulmonary function. Methods: Over 240 children with pulmonary complications, such as acute chest syndrome, reactive airway disease, and chronic hypoxia, have been evaluated in the Sickle Cell Pulmonary Clinic at Children’s Healthcare of Atlanta since beginning in July 2000. As part of the Clinic’s standard of care, PFT were routinely attempted on children over the age of 5. A retrospective review of PFT results was done for the children with SCA and prior abnormal PFT. Children were included in the HU cohort (+HU) if repeat PFTs were available following > 3 months on HU therapy and if time on HU did not include frequent RBC transfusions. Children without history of HU therapy (−HU) were selected for comparison. PFTs were performed on a standard plethysmograph. Paired t-test was used to evaluate observed differences. Results: Thirty-one children with prior abnormal PFT had test before and following prescription of HU. Their mean age was 12.6 (range 6–20) years and mean duration of HU was 21 (range 4–47) months at the time of the repeat PFT. Hematologic changes expected on HU occurred for all 31 children. Twenty-four children followed for abnormal PFT had no history of HU (−HU) and matched the +HU group by gender, age (mean 12.3, range 7–19 years), duration followed at time of repeat PFT (mean 19, range 3–66 months; p=0.36), and initial hematologic parameters. Spirometry findings changed for +HU group, and remained stable for −HU group. Mean FVC and FEV1 values improved significantly on HU, when compared to initial (PreHU) PFT and to −HU controls. Conversion to a normal PFT, as interpreted by a pediatric pulmonologist masked to treatment status, occurred in 18 (58%) and 2 (8%) children in the +HU and −HU groups, respectively. Table 1: Serial PFT and hematologic parameters according to HU exposure −HU (n=24) +HU (n=31) Initial Repeat # PreHU Repeat 1 % predicted value for age, sex and height of subject. 2Mean (SD) #No significant changes compared to Initial, p > 0.05. *P value < 0.001 compared to PreHU; ++P value < 0.001 compared to −HU repeat. PFT parameter 1 TLC 88 (13.6)2 85 (11.7) 85 (13.4) 90 (13.5) FVC 78 (9.8) 79 (9.9) 75 (12.6) 90 (13.2)*,++ FEV1 75 (9.6) 74 (12.2) 72 (11.4) 86 (10.2)*,++ FEF 25-75 75 (22) 72 (28.0) 77 (23.4) 79 (26.8) FEV1/FVC (%) 85(6.7) 82 (9.8) 87 (11.8) 86 (11.1) Pulse oximetry (%) 95 (3.1) 96 (2.4) 94 (4.4) 97 (2.8)* WBC (x103/ul) 14 (3.8) 13 (2.9) 13.02 (2.9) 9.0 (2.1) *,++ Hb (g/dl) 8.0 (0.1) 8.0 (0.9) 7.8 (1.1) 9.1 (1.3) *,++ MCV (fl) 84 (9.2) 85 (10.0) 87.3 (8.1) 101.2 (10.1) *,++ HbF (%) 4.3 (1.5) 5.2 (5.2) 6.0 (3.8) 14.0 (7.3) *,++ Conclusions: Serial PFTs showed improved pulmonary function, following initiation of HU therapy in children with prior abnormal PFT. Routine PFT assessments of children prescribed HU may serve as an objective measure of clinical response in children with SCA and pulmonary complications. These results will help in the design of future prospective studies examining the clinical benefits of HU therapy for children at risk for long-term pulmonary complications.

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Study of some Pulmonary Function Tests in Children with Sickle Cell Anemia: Correlation with Iron Overload

IOSR Journal of Pharmacy (IOSRPHR) ◽

10.9790/3013-0409031037 ◽

2014 ◽

Vol 4 (9) ◽

pp. 31-37

Author(s):

Adel A Hagag ◽

Mohamed S ElFarargy ◽

Yousef M Mansour

Keyword(s):

Iron Overload ◽

Pulmonary Function ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Pulmonary Function Tests ◽

Function Tests

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Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort

Blood ◽

10.1182/blood-2010-06-293514 ◽

2011 ◽

Vol 117 (4) ◽

pp. 1130-1140 ◽

Cited By ~ 191

Author(s):

Françoise Bernaudin ◽

Suzanne Verlhac ◽

Cécile Arnaud ◽

Annie Kamdem ◽

Sylvie Chevret ◽

...

Keyword(s):

Magnetic Resonance ◽

Sickle Cell ◽

Predictive Factors ◽

Sickle Cell Anemia ◽

Transcranial Doppler ◽

Stroke Risk ◽

Preventive Intervention ◽

Intensive Therapy ◽

Human Leukocyte ◽

Hazard Ratio

AbstractTranscranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sβ0), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 109/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.

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