Unrelated cord blood transplantation in children with sickle cell disease: Review of four‐center experience

Adamkiewicz, Thomas V.; Szabolcs, Paul; Haight, Ann E.; Baker, K. Scott; Staba, Susan; Kedar, Amos; Chiang, Kuang‐Yueh; Krishnamurti, Lakshmanan; Boyer, Michael W.; Kurtzberg, J.; Wagner, John E.; Wingard, John R.; Yeager, Andrew M.

doi:10.1111/j.1399-3046.2007.00725.x

Cited by 70 publications

(52 citation statements)

References 19 publications

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“…Indeed, it has been shown that UCB may not engraft after RIC in chemotherapy-naive patients. [25][26][27] However, it is expected that the patients enrolled in future trials will have received intensive chemotherapy before transplantation. First, this salvage approach is aimed at patients refractory to former chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Although it has been shown that a RIC regimen may lead to UCB engraftment in childhood leukemia, 24 some reports suggest that engraftment may be poor in patients with other diseases. [25][26][27] Only one previous patient with a solid tumor was reported to engraft successfully after RIC regimen and UCBT. 28 The objective of this pilot trial was therefore to examine engraftment after RIC of partially matched UCB in children with relapsed or refractory neuroblastoma.…”

Section: Introductionmentioning

confidence: 99%

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Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Jubert

Wall

Grimley

et al. 2010

Bone Marrow Transplant

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Relapsed or refractory neuroblastoma is uniformly fatal. We hypothesized that allogeneic response could provide a platform for immunotherapy in neuroblastoma. We therefore undertook a pilot trial of unrelated cord blood transplantation after reduced intensity conditioning regimen (RIC) in children with relapsed neuroblastoma to assess engraftment and tolerability in this heavily pretreated population. The RIC included CY (50 mg/kg, day À6), fludarabine (40 mg/m 2 , days À6 to À2), total body irradiation (200 cGy, day À1), and rabbit antithymocyte globulin (2.5 mg/kg, days À3 to À1). Six patients were enrolled: four were in partial responsive relapse, one with a mixed response and one in refractory relapse. All patients tolerated the regimen well and had donor engraftment with full neutrophil and plt recovery (median time 12 and 35 days, respectively). One patient never experienced neutropenia and another did not need plt transfusions. All patients progressed after transplant (median time 55 days, 26-180 days). Natural killer (NK) cell counts were normal within 2 months, whereas T-cell recovery was slower. In conclusion, unrelated cord blood engrafts after RIC in children with refractory neuroblastoma. Future research should be aimed at transplanting patients with minimal residual disease, using less intensive immunosuppression and adding NK-cell based post transplant immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Jubert

Wall

Grimley

et al. 2010

Bone Marrow Transplant

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“…This study was limited in sample size and indicates that a prospective, multicenter trial with similar treatment guidelines might be more effective and informative. 34 Reduced intensity conditioning regimens Efforts to expand the application of HCT for SCD and thalassemia have been restricted not only by lacking suitable donors, but also by the risk of significant toxicity that accompanies this intensive procedure. 35 A recent review of 175 SCD patients treated by conventional HCT observed complications of GR and disease recurrence in 16 patients (9%) with 17 patients (9%) dying of transplantrelated causes.…”

Section: Indicationsmentioning

confidence: 99%

Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future

Bhatia

Walters²

2007

Bone Marrow Transplant

123

112

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b-Thalassemia major and sickle cell disease (SCD) are among the most common hereditary disorders worldwide. The supportive treatment of b-thalassemia major requires chronic, life-long RBC transfusions, which cause progressive iron overload and the potential for impaired endocrine, cardiac and hepatic function. The phenotype of thalassemia major is reliably predicted by its genotype. In contrast, SCD is a variable genetic disease caused by a single amino acid substitution in the b chain of human hemoglobin. Manifestations of SCD are quite varied, but generally result from the tendency of Hb S to irreversibly polymerize under physiologic stressors such as hypoxemia and acidosis. The polymerization causes perturbations in the erythrocyte integrity that promote vaso-occlusion and which manifest as clinical events such as severe painful episodes, acute chest syndrome, splenic infarction, stroke and avascular necrosis of target joints. The only cure proved for these disorders is correction of the genetic defect by allogeneic hematopoietic cell transplantation (HCT). We illustrate the pediatric experience of HCT for hemoglobinopathies and discuss how these results affect future therapeutic decisions in children who inherit these disorders. Bone Marrow Transplantation (2008) 41, 109-117; doi:10.1038/sj.bmt.1705943; published online 3 December 2007 Keywords: hematopoietic cell transplantation; hemoglobinopathies; children; sickle cell disease; thalassemia Introduction b-Thalassemia major and sickle cell disease (SCD) are hereditary anemias that decrease lifespan and reduce the quality of life. While supportive therapies are available that minimize long-term sequelae, the only cure for these disorders is allogeneic hematopoietic cell transplantation (HCT). While the outcomes after HCT are quite similar in both disorders, the decision about when and if to pursue HCT follows very different time-lines. All patients with thalassemia are at risk for transfusion-related iron overload and its attendant negative impact on clinical well-being. As a result, many clinicians strongly consider HCT as a therapeutic option in children who are less than 17 years of age and who have an HLA-identical sibling donor, due to the excellent results of HCT in this setting. However, in patients with SCD, the clinical symptoms are diverse and most clinicians delay HCT until there is evidence of severe disease, such as in those who have had a stroke, even though the results after HCT for SCD are very similar to results after HCT for thalassemia. This review presents the current state-of-the-art of HCT for b-thalassemia and SCD and discusses future directions that might improve survival and decrease morbidity. b-Thalassemia major BackgroundThalassemias result from mutations of the globin genes that cause reduced or absent hemoglobin production, reducing oxygen delivery. 1 The thalassemias are the most common single-gene disorders, with 4.83% of the world population carrying a globin gene variant. 2 To treat the anemia and restore oxygen delivery to...

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“…In unrelated CBT, although more feasible for pediatric patients on the basis of the availability of 4/6 HLA-matched cord blood unit, it appears to be associated with a great risk of graft rejection and GVHD. The largest study consisting of seven patients reported one death, an EFS of 43%, five patients developed acute GVHD, and one patient chronic GVHD (Adamkiewicz et al 2007). Moreover, CBT for adults is limited by the necessary total nucleated cell count per kilogram of body weight for engraftment to occur.…”

Section: Hematopoietic Stem Cell Transplantation For Sickle Cell Diseasementioning

confidence: 99%

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

Lucarelli

Isgrò²,

Sodani³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

141

106

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The globally widespread single-gene disorders b-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class-based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel nonmyeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation.

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Unrelated cord blood transplantation in children with sickle cell disease: Review of four‐center experience

Cited by 70 publications

References 19 publications

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

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