Stem Cell Transplantation in Sickle Cell Disease

Treat allogeneic hematopoietic cell transplantation (HCT) as a curative option rather than escalation of acute-care management. Matched-sibling HCT is the best-established donor strategy for sickle cell disease (SCD), with reported overall survival of 95% and high event-free survival in children in a Lancet Haematology review. BMJ+1BMJSickle cell disease in children: an update of the evidence in lowThe LancetThe role of haematopoietic stem cell transplantation for ...

Initiate transplant discussion early for a symptomatic child or young adult with an HLA-identical sibling donor rather than waiting for additional irreversible complications. Expert recommendations cited in current reviews favor transplanting symptomatic young patients with an HLA-identical sibling as early as possible, preferably at preschool age; registry data also associate transplantation at age 12 years or younger with improved event-free survival. The Lancet+1The LancetEffect of donor type and conditioning regimen intensity on ...ScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect

Frame the decision against the alternative of ongoing disease-modifying and supportive care. Hydroxyurea, L-glutamine, voxelotor, and crizanlizumab can reduce vaso-occlusive events or severe complications but are not curative; HCT introduces risks of conditioning-related mortality, infertility or gonadal failure, graft-versus-host disease (GVHD), and graft failure. ScienceDirect+1ScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirectema europa euXromi, INN-hydroxycarbamide - EMA

Perform donor identification and high-resolution HLA assessment early. For unrelated donor selection, HLA-A, HLA-B, HLA-C, and HLA-DRB1 matching defines an 8/8 match in National Marrow Donor Program recommendations summarized in a current review. ScienceDirectScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect A potential matched sibling donor should be evaluated alongside the recipient before a patient is labeled ineligible because few SCD candidates have access to this donor type. The Lancet+1The LancetEffect of increased dose of total body irradiation on graft failure ...ScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect

Document pre-existing HLA antibodies and red-cell alloimmunization before HCT. These immunologic exposures are specifically studied as pretransplant variables in SCD transplantation and should trigger coordinated transfusion-medicine and transplant planning rather than ad hoc peri-transplant transfusion decisions. The LancetThe LancetThe impact of pre-existing HLA and red blood cell ...

Counsel explicitly that conditioning intensity and donor source trade donor-engraftment reliability against toxicity. Myeloablative matched-sibling HCT in children has excellent outcomes, whereas reduced-intensity approaches are associated with more mixed chimerism; haploidentical protocols have variable graft-failure and chronic-GVHD rates. ScienceDirect+2ScienceDirectRelationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease - ScienceDirectASHThe range of haploidentical transplant protocols in sickle cell ...ema europa euXromi, INN-hydroxycarbamide - EMA

For children with a matched sibling donor, myeloablative HCT remains the benchmark approach described as having excellent outcomes. ASHASHThe range of haploidentical transplant protocols in sickle cell ... Bone marrow and HLA-identical sibling cord blood are the recommended stem-cell sources in expert recommendations summarized in review literature. ScienceDirectScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect The expected benefit is durable donor erythropoiesis and elimination of SCD manifestations, but counseling must include acute transplant toxicity and later infertility, gonadal failure, GVHD, and graft failure. ScienceDirect+1ScienceDirectRelationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease - ScienceDirectema europa euXromi, INN-hydroxycarbamide - EMA

For an HLA-matched unrelated donor, distinguish fully matched from mismatched donor options. FDA advisory analyses in a different transplant context found outcomes with matched unrelated donors comparable to those with a matched donor strategy, while mismatched donors had frequent early events driven largely by second transplantation for graft failure; this reinforces avoiding extrapolation from matched-unrelated to mismatched-donor risk. fdafdaCellular, Tissue, and Gene Therapies Advisory Committee June ... In SCD, use an 8/8 unrelated-donor match when pursuing this pathway and review conditioning and graft source within the transplant program. ScienceDirectScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect

For haploidentical HCT, transplant protocol choice is a clinical determinant, not a technical detail. Published review describes a range of haploidentical protocols, and an EBMT meeting report notes markedly worse outcomes in participants younger than 18 years than in adults, with graft failure reported in 15% to 25% and chronic GVHD up to 30% in pediatric recipients. Nature+1NatureThe 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians – Poster Session (P001-P972) | Bone Marrow TransplantationASHThe range of haploidentical transplant protocols in sickle cell ... These estimates should be presented as protocol- and cohort-specific, rather than as universal rates for every haploidentical platform.

Measure donor-recipient chimerism serially after HCT and pair its interpretation with hemoglobin S (HbS) measurement and clinical recurrence. In a retrospective SCD cohort with assessments at day 100 and at 1 and 2 years, recurrent disease was defined by vaso-occlusive crises, acute chest syndrome, stroke, and/or HbS greater than 50%. ScienceDirectScienceDirectRelationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease - ScienceDirect This makes HbS trajectory and recurrence of SCD events clinically relevant alongside the percentage of donor cells.

Do not intervene for mixed chimerism solely because it is present. In the same cohort, donor chimerism greater than 25% or HbS less than 50% was associated with freedom from SCD symptoms; the lowest donor chimerism documented without symptomatic disease was 26%. ScienceDirectScienceDirectRelationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease - ScienceDirect By contrast, donor chimerism below 10% was defined as graft failure in that analysis. ScienceDirectScienceDirectRelationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease - ScienceDirect

Request lineage-specific chimerism rather than relying only on whole-blood results when a T-cell-depleted graft has been used. Whole-blood mixed chimerism driven by the T-cell lineage was not associated with adverse outcomes in a pediatric study and resolved without immunosuppression adjustment or donor lymphocyte infusion; intervention decisions should be based on lineage-specific results. ScienceDirectScienceDirectDonor-Host Lineage-Specific Chimerism Monitoring and Analysis in Pediatric Patients Following Allogeneic Stem Cell Transplantation: Influence of Pretransplantation Variables and Correlation with Post-Transplantation Outcomes - ScienceDirect

The counseling conversation should compare the patient’s current disease burden and expected trajectory with a one-time transplant risk profile. HCT can cure SCD and has been reported to improve quality of life in high-risk patients, but it may cause mortality, GVHD, infertility, gonadal failure, and graft failure. BMJ+1BMJSickle cell disease in children: an update of the evidence in lowema europa euXromi, INN-hydroxycarbamide - EMA The appropriate decision is therefore individualized rather than based solely on whether a donor can be found.

For a matched sibling donor, explain that this approach has the clearest evidence base and is generally favored early in symptomatic pediatric disease. The Lancet+2The LancetThe role of haematopoietic stem cell transplantation for ...The LancetEffect of donor type and conditioning regimen intensity on ...ScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirect For patients without a matched sibling, explicitly describe that alternate donor strategies may provide access to cure but have more uncertain and protocol-dependent risk, including pediatric haploidentical graft failure and chronic GVHD. Nature+2NatureThe 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians – Poster Session (P001-P972) | Bone Marrow TransplantationScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirectASHThe range of haploidentical transplant protocols in sickle cell ...

Continue longitudinal reassessment if HCT is deferred. Donor availability, transplant-platform experience, and the balance between progressive SCD complications and treatment-related toxicity can change over time; a prior decision not to transplant should not preclude renewed transplant review. ScienceDirect+2ScienceDirectCURATIVE TREATMENT OPTIONS IN SICKLE CELL DISEASE - ScienceDirectASHThe range of haploidentical transplant protocols in sickle cell ...ASHInformed shared decision-making or rigid eligibility and ...