From www.bloodjournal.org by guest on September 11, 2016. For personal use only. 416
BLOOD, 8 JANUARY 2015 x VOLUME 125, NUMBER 2
CORRESPONDENCE
To the editor: Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease Individuals with hemoglobin (Hb) SC disease have fewer vasoocclusive events and greater life expectancy than those with Hb SS, and they have been excluded from most interventional clinical trials. Although the 10% prevalence of overt stroke and .35% prevalence of silent cerebral infarctions (SCIs) in Hb SS disease is well described, less is known about neurologic complications in children with Hb SC. We sought to determine the prevalence of SCIs in our cohort of 96 children with Hb SC disease. In this cohort, the prevalence of SCIs was 13.5%, much higher than expected based on the Cooperative Study of Sickle Cell Disease (CSSCD).1 We identified all children with Hb SC or Hb SS, ages 6 to 21 years, at our institution between January 2004 and May 2012. In 2006, our institution began screening all children at least 6 years of age with sickle cell disease for SCIs, regardless of neurologic symptoms. Clinical magnetic resonance imaging (MRI) data or magnetic resonance angiograms were available in 96/123 children with Hb SC and 168/181 children with Hb SS. Children ages 6 years and older without an MRI were excluded from analysis. MRIs were performed on 1.5 T or 3 T Siemens MRI scanners, with standard sagittal T1, axial and coronal fluid-attenuated inversion recovery (FLAIR), axial T2 turbo spin echo, susceptibility-weighted and 12-direction diffusionweighted sequences. Cerebral infarctions were defined as T2- or FLAIR-weighted hyperintensities at least 3 mm in diameter, identified in 2 planes.2 All reports were reviewed, and one investigator (K.P.G.) reviewed all images with possible SCIs noted in the report. Documented absence of neurologic symptoms that correlated with lesion location in the medical record qualified a lesion as an SCI. Lesion characteristics were compared with a Pearson’s x2 or Fisher’s exact test. SCIs were found in 13/96 (13.5%) children with Hb SC, with a median age of 12.2 years (range, 6.2-19.3 years). No children with Hb SC had overt strokes. In contrast, 72/168 children with Hb SS disease (42.9%) had cerebral infarction: 5/168 (3.0%) had a history of overt strokes without SCIs, 21/168 (12.5%) had overt strokes plus SCIs, and 46 (27.4%) had SCIs only. Infarct lesion location and number were similar between children with Hb SC and Hb SS (Table 1). In this retrospective cohort of 96 children with Hb SC, SCI prevalence was 13.5%, more than double the 5.8% (7/120) prevalence reported in the CSSCD.1 Although children with Hb SC typically have fewer disease manifestations than those with Hb SS, this rate of potentially unnoticed brain injury appears to be higher than incidental white matter lesions in children with migraine (6% to
Table 1. Silent cerebral infarction characteristics on MRI Hb SC (n 5 13)
Hb SS (n 5 67)
P
Bilateral SCI
9 (69)
44 (66)
.804
One-sided SCI only
4 (31)
23 (34)
Frontal lobe
11 (85)
64 (95)
.184*
Parietal lobe
6 (46)
38 (57)
.484
1-5 lesions total
7 (54)
30 (45)
.762
6-10 lesions total
4 (31)
21 (31)
.11 lesions total
2 (15)
16 (24)
Location
10%)3 or healthy children (1.3%).4 In our Hb SS comparison group, the SCI prevalence was comparable to recent cohorts,2,5 indicating that our center is not biased toward SCI detection. The CSSCD used T1- and T2-weighted sequences on 0.6, 1, or 1.5 T MRI,6 as opposed to FLAIR sequences on 1.5 or 3 T MRI currently in clinical use. Therefore, greater SCI prevalence in recent reports2,5 may be due in part to technological improvements. The pathophysiology of SCIs is presumed to involve red blood cell (RBC) sickling and vaso-occlusion in small cerebral vessels based on postmortem examinations.7 Transient hypoperfusion, hypoxemia, anemia, and cerebral vasculopathy may also contribute,8 but the mechanisms of SCIs may differ between children with Hb SC and Hb SS. In people with sickle cell disease, blood viscosity is higher compared with controls, especially at higher hemoglobin concentration; reduced RBC deformability and increased RBC aggregate formation also contribute to vaso-occlusion.9 Higher baseline hemoglobin, and thus higher blood viscosity, in Hb SC may contribute to small-vessel occlusion in these children. In Hb SS, both overt strokes and SCIs are associated with more severe anemia, but overt strokes are rare in Hb SC. Perhaps in children with Hb SC, the higher hemoglobin concentration minimizes overt stroke risk but the accompanying viscosity increase predisposes to small-vessel occlusion and SCIs in a subset of patients. Investigations of cerebral blood flow and cerebral oxygen utilization may identify mechanisms of SCIs in children with Hb SC and Hb SS. SCIs are correlated with decreased intellectual functioning and greater overt stroke risk in children with Hb SS, but their impact is unestablished in Hb SC. Likewise, there is no known treatment of SCIs in Hb SC. Although blood transfusion therapy reduces recurrence of SCIs and overt strokes in children with Hb SS,2,10 the SCI recurrence risk in Hb SC is unknown. Furthermore, the risk-benefit balance of transfusion therapy in Hb SC is likely different than in Hb SS, given the absence of severe anemia and lower frequency of vasoocclusive pain and hospitalizations in children with Hb SC. Therefore, transfusion therapy for children with Hb SC and SCIs cannot be advocated currently. Clinical risk factors, consequences, and potential treatments of SCIs in Hb SC should be investigated prospectively. Kristin P. Guilliams Division of Pediatric and Developmental Neurology, Department of Neurology, and Division of Critical Care, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO Melanie E. Fields Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO Monica L. Hulbert Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
Lesion burden
Values are n (%) unless otherwise indicated. *Fisher’s exact test.
Acknowledgments: This work was supported by the National Institutes of Health, National Center for Advancing Translational Science grant ICTS UL1TR000448 (K.P.G. and M.E.F.) and National Institute of Neurological Disorders and Stroke grant T32 NS007205-32S1 (K.P.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
From www.bloodjournal.org by guest on September 11, 2016. For personal use only. BLOOD, 8 JANUARY 2015 x VOLUME 125, NUMBER 2
Contribution: K.P.G. and M.L.H. designed research and collected data; M.E.F. and M.L.H. did statistical analysis; and K.P.G., M.E.F., and M.L.H. wrote and edited the manuscript. Conflict-of-interest disclosure: The authors declare no competing financial interests. Correspondence: Kristin Guilliams, Departments of Neurology and Pediatrics, Washington University in St. Louis School of Medicine, 660 South Euclid Ave, Box 8111, St. Louis, MO 63110; e-mail: [email protected].
References 1. Pegelow CH, Macklin EA, Moser FG, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood. 2002;99(8):3014-3018. 2. DeBaun MR, Gordon M, McKinstry RC, et al. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014;371(8):699-710. 3. Mar S, Kelly JE, Isbell S, Aung WY, Lenox J, Prensky A. Prevalence of white matter lesions and stroke in children with migraine. Neurology. 2013;81(16): 1387-1391.
CORRESPONDENCE
417
4. Kim BS, Illes J, Kaplan RT, Reiss A, Atlas SW. Incidental findings on pediatric MR images of the brain. AJNR Am J Neuroradiol. 2002;23(10):1674-1677. 5. Bernaudin F, Verlhac S, Arnaud C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood. 2011;117(4):1130-1140, quiz 1436. 6. Moser FG, Miller ST, Bello JA, et al. The spectrum of brain MR abnormalities in sickle-cell disease: a report from the Cooperative Study of Sickle Cell Disease. AJNR Am J Neuroradiol. 1996;17(5):965-972. 7. Rothman SM, Fulling KH, Nelson JS. Sickle cell anemia and central nervous system infarction: a neuropathological study. Ann Neurol. 1986;20(6):684-690. 8. Dowling MM, Quinn CT, Plumb P, et al. Acute silent cerebral ischemia and infarction during acute anemia in children with and without sickle cell disease. Blood. 2012;120(19):3891-3897. 9. Tripette J, Alexy T, Hardy-Dessources MD, et al. Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease. Haematologica. 2009;94(8):1060-1065. 10. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339(1):5-11.
© 2015 by The American Society of Hematology
To the editor: HLA-matched related-donor HSCT in Fanconi anemia patients conditioned with cyclophosphamide and fludarabine Fanconi anemia (FA) is a rare, phenotypically heterogeneous inherited disorder clinically characterized by congenital abnormalities, progressive bone marrow failure (BMF), and a predisposition to develop malignancies.1 Hematopoietic stem cell transplantation (HSCT) is the only curative option for FA patients.2,3 However, finding the best conditioning regimen is still challenging for clinicians. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning through non-irradiation-based regimens.4-9 A reduced conditioning regimen based on CY (60 mg/kg) alone was proposed by Bomfim et al.10 Survival rates were excellent, but some patients experienced primary (n 5 1) or late (n 5 4) graft failure (11% of the patients). Moreover, mucositis was a major problem, in that 25 patients (60%) presented grade 3/4 mucositis. The cumulative incidence of chronic graft-versus-host disease (GVHD) was 29%. We hypothesized that tapering the dose of CY to 40 mg/kg and adding fludarabine (FLU) at 90 mg/m2 might improve engraftment, decrease GVHD rates, and eventually improve overall toxicity in FA patients transplanted with human leukocyte antigen (HLA)-matched siblings.
Figure 1. Overall survival after HLA-matched related-donor HSCT conditioned with CY and FLU in FA patients (n 5 20).
In 2004, the French reference center for aplastic anemia and the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) recommended using FLU at 90 mg/m2 (30 mg/m2 on days 24, 23, and 22) and CY at 40 mg/kg (10 mg/kg on days 25, 24, 23, and 22) for FA patients transplanted from a matched family donor. Indication for transplantation was based on hematologic complications (transfusions and/or infections). FA patients with morphologic signs of clonal evolution (myelodysplastic syndrome or acute myeloid leukemia) were excluded from the study. All patients in France who received a first allogenic HSCT for FA from a matched related donor between October 2004 and January 2013 using this approach were analyzed (n 5 20). Clinical data were prospectively collected using Project Manager Internet Server, an Internet-based data registry system shared by all SFGM-TC centers. Cyclosporin A and mycophenolate mofetil were used as GVHD prophylaxis. Six patients received an in vivo T-cell depletion using antithymocyte globulin because of local policy at their center. The guidelines were approved by the Saint-Louis Hospital Ethics Committee. The median age at HSCT was 9 years (range 6-19). Stem cell source was bone marrow in 16 cases and matched related cord blood in the remaining transplants. None of the patients received peripheral blood stem cells. All patients had severe or moderate BMF (median hemoglobin: 8.9 g/dL; median platelets: 31 3 103/mL; median neutrophils: 0.88 3 103/mL) at the time of HSCT. Two patients had chromosomal abnormalities (47,XX,i(1)(q10)[10]/48,idem,18[3] and 47,XX,1der(1;3)(q10;q10)[14]/46,XX[6]); however, neither developed overt myelodysplasia/leukemia before transplant. Patients belonged to complementation groups FANC-A (n 5 17) and FANC-G (n 5 2). Transplants were performed within a median of 30 months (range 7-143) from FA diagnosis. A median of 3.8. 3 108 nucleated marrow cells were infused (range 0.65-8.97). Within a median follow up of 2 years (range 0.2-7.4), overall survival was 95% (Figure 1). Only one patient with an atypical form of FA associated with severe immunodeficiency prior to transplant
From www.bloodjournal.org by guest on September 11, 2016. For personal use only.
2015 125: 416-417 doi:10.1182/blood-2014-10-605964
Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease Kristin P. Guilliams, Melanie E. Fields and Monica L. Hulbert
Updated information and services can be found at: http://www.bloodjournal.org/content/125/2/416.full.html Articles on similar topics can be found in the following Blood collections Clinical Trials and Observations (4389 articles) Pediatric Hematology (478 articles) Red Cells, Iron, and Erythropoiesis (728 articles) Sickle Cell Disease (123 articles) Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
BLOOD, 8 JANUARY 2015 x VOLUME 125, NUMBER 2
CORRESPONDENCE
To the editor: Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease Individuals with hemoglobin (Hb) SC disease have fewer vasoocclusive events and greater life expectancy than those with Hb SS, and they have been excluded from most interventional clinical trials. Although the 10% prevalence of overt stroke and .35% prevalence of silent cerebral infarctions (SCIs) in Hb SS disease is well described, less is known about neurologic complications in children with Hb SC. We sought to determine the prevalence of SCIs in our cohort of 96 children with Hb SC disease. In this cohort, the prevalence of SCIs was 13.5%, much higher than expected based on the Cooperative Study of Sickle Cell Disease (CSSCD).1 We identified all children with Hb SC or Hb SS, ages 6 to 21 years, at our institution between January 2004 and May 2012. In 2006, our institution began screening all children at least 6 years of age with sickle cell disease for SCIs, regardless of neurologic symptoms. Clinical magnetic resonance imaging (MRI) data or magnetic resonance angiograms were available in 96/123 children with Hb SC and 168/181 children with Hb SS. Children ages 6 years and older without an MRI were excluded from analysis. MRIs were performed on 1.5 T or 3 T Siemens MRI scanners, with standard sagittal T1, axial and coronal fluid-attenuated inversion recovery (FLAIR), axial T2 turbo spin echo, susceptibility-weighted and 12-direction diffusionweighted sequences. Cerebral infarctions were defined as T2- or FLAIR-weighted hyperintensities at least 3 mm in diameter, identified in 2 planes.2 All reports were reviewed, and one investigator (K.P.G.) reviewed all images with possible SCIs noted in the report. Documented absence of neurologic symptoms that correlated with lesion location in the medical record qualified a lesion as an SCI. Lesion characteristics were compared with a Pearson’s x2 or Fisher’s exact test. SCIs were found in 13/96 (13.5%) children with Hb SC, with a median age of 12.2 years (range, 6.2-19.3 years). No children with Hb SC had overt strokes. In contrast, 72/168 children with Hb SS disease (42.9%) had cerebral infarction: 5/168 (3.0%) had a history of overt strokes without SCIs, 21/168 (12.5%) had overt strokes plus SCIs, and 46 (27.4%) had SCIs only. Infarct lesion location and number were similar between children with Hb SC and Hb SS (Table 1). In this retrospective cohort of 96 children with Hb SC, SCI prevalence was 13.5%, more than double the 5.8% (7/120) prevalence reported in the CSSCD.1 Although children with Hb SC typically have fewer disease manifestations than those with Hb SS, this rate of potentially unnoticed brain injury appears to be higher than incidental white matter lesions in children with migraine (6% to
Table 1. Silent cerebral infarction characteristics on MRI Hb SC (n 5 13)
Hb SS (n 5 67)
P
Bilateral SCI
9 (69)
44 (66)
.804
One-sided SCI only
4 (31)
23 (34)
Frontal lobe
11 (85)
64 (95)
.184*
Parietal lobe
6 (46)
38 (57)
.484
1-5 lesions total
7 (54)
30 (45)
.762
6-10 lesions total
4 (31)
21 (31)
.11 lesions total
2 (15)
16 (24)
Location
10%)3 or healthy children (1.3%).4 In our Hb SS comparison group, the SCI prevalence was comparable to recent cohorts,2,5 indicating that our center is not biased toward SCI detection. The CSSCD used T1- and T2-weighted sequences on 0.6, 1, or 1.5 T MRI,6 as opposed to FLAIR sequences on 1.5 or 3 T MRI currently in clinical use. Therefore, greater SCI prevalence in recent reports2,5 may be due in part to technological improvements. The pathophysiology of SCIs is presumed to involve red blood cell (RBC) sickling and vaso-occlusion in small cerebral vessels based on postmortem examinations.7 Transient hypoperfusion, hypoxemia, anemia, and cerebral vasculopathy may also contribute,8 but the mechanisms of SCIs may differ between children with Hb SC and Hb SS. In people with sickle cell disease, blood viscosity is higher compared with controls, especially at higher hemoglobin concentration; reduced RBC deformability and increased RBC aggregate formation also contribute to vaso-occlusion.9 Higher baseline hemoglobin, and thus higher blood viscosity, in Hb SC may contribute to small-vessel occlusion in these children. In Hb SS, both overt strokes and SCIs are associated with more severe anemia, but overt strokes are rare in Hb SC. Perhaps in children with Hb SC, the higher hemoglobin concentration minimizes overt stroke risk but the accompanying viscosity increase predisposes to small-vessel occlusion and SCIs in a subset of patients. Investigations of cerebral blood flow and cerebral oxygen utilization may identify mechanisms of SCIs in children with Hb SC and Hb SS. SCIs are correlated with decreased intellectual functioning and greater overt stroke risk in children with Hb SS, but their impact is unestablished in Hb SC. Likewise, there is no known treatment of SCIs in Hb SC. Although blood transfusion therapy reduces recurrence of SCIs and overt strokes in children with Hb SS,2,10 the SCI recurrence risk in Hb SC is unknown. Furthermore, the risk-benefit balance of transfusion therapy in Hb SC is likely different than in Hb SS, given the absence of severe anemia and lower frequency of vasoocclusive pain and hospitalizations in children with Hb SC. Therefore, transfusion therapy for children with Hb SC and SCIs cannot be advocated currently. Clinical risk factors, consequences, and potential treatments of SCIs in Hb SC should be investigated prospectively. Kristin P. Guilliams Division of Pediatric and Developmental Neurology, Department of Neurology, and Division of Critical Care, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO Melanie E. Fields Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO Monica L. Hulbert Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
Lesion burden
Values are n (%) unless otherwise indicated. *Fisher’s exact test.
Acknowledgments: This work was supported by the National Institutes of Health, National Center for Advancing Translational Science grant ICTS UL1TR000448 (K.P.G. and M.E.F.) and National Institute of Neurological Disorders and Stroke grant T32 NS007205-32S1 (K.P.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
From www.bloodjournal.org by guest on September 11, 2016. For personal use only. BLOOD, 8 JANUARY 2015 x VOLUME 125, NUMBER 2
Contribution: K.P.G. and M.L.H. designed research and collected data; M.E.F. and M.L.H. did statistical analysis; and K.P.G., M.E.F., and M.L.H. wrote and edited the manuscript. Conflict-of-interest disclosure: The authors declare no competing financial interests. Correspondence: Kristin Guilliams, Departments of Neurology and Pediatrics, Washington University in St. Louis School of Medicine, 660 South Euclid Ave, Box 8111, St. Louis, MO 63110; e-mail: [email protected].
References 1. Pegelow CH, Macklin EA, Moser FG, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood. 2002;99(8):3014-3018. 2. DeBaun MR, Gordon M, McKinstry RC, et al. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014;371(8):699-710. 3. Mar S, Kelly JE, Isbell S, Aung WY, Lenox J, Prensky A. Prevalence of white matter lesions and stroke in children with migraine. Neurology. 2013;81(16): 1387-1391.
CORRESPONDENCE
417
4. Kim BS, Illes J, Kaplan RT, Reiss A, Atlas SW. Incidental findings on pediatric MR images of the brain. AJNR Am J Neuroradiol. 2002;23(10):1674-1677. 5. Bernaudin F, Verlhac S, Arnaud C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood. 2011;117(4):1130-1140, quiz 1436. 6. Moser FG, Miller ST, Bello JA, et al. The spectrum of brain MR abnormalities in sickle-cell disease: a report from the Cooperative Study of Sickle Cell Disease. AJNR Am J Neuroradiol. 1996;17(5):965-972. 7. Rothman SM, Fulling KH, Nelson JS. Sickle cell anemia and central nervous system infarction: a neuropathological study. Ann Neurol. 1986;20(6):684-690. 8. Dowling MM, Quinn CT, Plumb P, et al. Acute silent cerebral ischemia and infarction during acute anemia in children with and without sickle cell disease. Blood. 2012;120(19):3891-3897. 9. Tripette J, Alexy T, Hardy-Dessources MD, et al. Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease. Haematologica. 2009;94(8):1060-1065. 10. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339(1):5-11.
© 2015 by The American Society of Hematology
To the editor: HLA-matched related-donor HSCT in Fanconi anemia patients conditioned with cyclophosphamide and fludarabine Fanconi anemia (FA) is a rare, phenotypically heterogeneous inherited disorder clinically characterized by congenital abnormalities, progressive bone marrow failure (BMF), and a predisposition to develop malignancies.1 Hematopoietic stem cell transplantation (HSCT) is the only curative option for FA patients.2,3 However, finding the best conditioning regimen is still challenging for clinicians. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning through non-irradiation-based regimens.4-9 A reduced conditioning regimen based on CY (60 mg/kg) alone was proposed by Bomfim et al.10 Survival rates were excellent, but some patients experienced primary (n 5 1) or late (n 5 4) graft failure (11% of the patients). Moreover, mucositis was a major problem, in that 25 patients (60%) presented grade 3/4 mucositis. The cumulative incidence of chronic graft-versus-host disease (GVHD) was 29%. We hypothesized that tapering the dose of CY to 40 mg/kg and adding fludarabine (FLU) at 90 mg/m2 might improve engraftment, decrease GVHD rates, and eventually improve overall toxicity in FA patients transplanted with human leukocyte antigen (HLA)-matched siblings.
Figure 1. Overall survival after HLA-matched related-donor HSCT conditioned with CY and FLU in FA patients (n 5 20).
In 2004, the French reference center for aplastic anemia and the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) recommended using FLU at 90 mg/m2 (30 mg/m2 on days 24, 23, and 22) and CY at 40 mg/kg (10 mg/kg on days 25, 24, 23, and 22) for FA patients transplanted from a matched family donor. Indication for transplantation was based on hematologic complications (transfusions and/or infections). FA patients with morphologic signs of clonal evolution (myelodysplastic syndrome or acute myeloid leukemia) were excluded from the study. All patients in France who received a first allogenic HSCT for FA from a matched related donor between October 2004 and January 2013 using this approach were analyzed (n 5 20). Clinical data were prospectively collected using Project Manager Internet Server, an Internet-based data registry system shared by all SFGM-TC centers. Cyclosporin A and mycophenolate mofetil were used as GVHD prophylaxis. Six patients received an in vivo T-cell depletion using antithymocyte globulin because of local policy at their center. The guidelines were approved by the Saint-Louis Hospital Ethics Committee. The median age at HSCT was 9 years (range 6-19). Stem cell source was bone marrow in 16 cases and matched related cord blood in the remaining transplants. None of the patients received peripheral blood stem cells. All patients had severe or moderate BMF (median hemoglobin: 8.9 g/dL; median platelets: 31 3 103/mL; median neutrophils: 0.88 3 103/mL) at the time of HSCT. Two patients had chromosomal abnormalities (47,XX,i(1)(q10)[10]/48,idem,18[3] and 47,XX,1der(1;3)(q10;q10)[14]/46,XX[6]); however, neither developed overt myelodysplasia/leukemia before transplant. Patients belonged to complementation groups FANC-A (n 5 17) and FANC-G (n 5 2). Transplants were performed within a median of 30 months (range 7-143) from FA diagnosis. A median of 3.8. 3 108 nucleated marrow cells were infused (range 0.65-8.97). Within a median follow up of 2 years (range 0.2-7.4), overall survival was 95% (Figure 1). Only one patient with an atypical form of FA associated with severe immunodeficiency prior to transplant
From www.bloodjournal.org by guest on September 11, 2016. For personal use only.
2015 125: 416-417 doi:10.1182/blood-2014-10-605964
Higher-than-expected prevalence of silent cerebral infarcts in children with hemoglobin SC disease Kristin P. Guilliams, Melanie E. Fields and Monica L. Hulbert
Updated information and services can be found at: http://www.bloodjournal.org/content/125/2/416.full.html Articles on similar topics can be found in the following Blood collections Clinical Trials and Observations (4389 articles) Pediatric Hematology (478 articles) Red Cells, Iron, and Erythropoiesis (728 articles) Sickle Cell Disease (123 articles) Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
