I have recently seen a 17 year-old young woman with SCD, who came in for a consultation with her mother. She has a brother without Sickle Cell Disease (SCD) or trait that is her HLA match, and she is considering HCT (hematopoietic cell transplantation: aka bone marrow transplant). Due to the incidence of ovarian failure from medications to prevent rejection of the graft (i.e. busulfan), she was referred to consider fertility preservation with egg freezing prior to this treatment. The dilemma, or gamble, for her is her future fertility vs. the development of severe effects of SCD if she does not have HCT or the side effects from HCT such as GVHD (graft versus host disease).
Treatment: Bone marrow transplant, aka HCT (hematopoietic cell transplantation) and SCD
Sickle disease is a devastating illness, but the clinical course is variable, and therefore prognostic factors to predict and advise patients whether they will experience severe symptoms from their disease are lacking. Since there is potential great benefits, as well as, serious side effects to this treatment, counseling needs to be very individualized.
Siblings are always preferable as HCT donors for individuals with SCD because of the lower risks of graft-versus-host disease (GVHD, graft failure or rejection with a related donor transplant. Siblings without sickle cell syndrome and those with sickle cell trait are acceptable as donors. The first patient with SCD to be treated with HCT was an 8 year old girl who had both AML (acute myeloblastic leukemia) and vasoocclusive crises. After HCT, in addition to having a normal bone marrow with no evidence for AML, her hemoglobin S level decreased to the level of the donor, who had sickle cell trait, and she had no further vasoocclusive crises. Additional studies with a larger numbers of patients were reported from Belgium and France. In 2000, a U. S. multi-center study reported on 50 children who received HCT from HLA-identical siblings. At 39 months of follow-up, overall survival was 94% and event-free survival 84%.
Long term (2 years of follow-up in 26 children) side effects of HCT were: 10 of 10 engrafted patients with a history of stroke all showed stable or improved findings on repeat magnetic resonance imaging of the brain. Linear growth scores were 100%, demonstrating a good to excellent quality of life. However, 4 of 7 females that were evaluated had impaired ovarian function, likely an effect of busulfan treatment. 3 of 26 patients in the late-effects cohort developed grade I to III acute GCHD after transplant, and 2 had chronic GCHD. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported results of myeloablative HCT from HLA matched sibling donors in 67 patients with SCD from 1989 to 2002. Average age at transplant was 10 years (range: 2-27). 5-year probabilities of overall and disease-free survival were 97 and 85 % respectively.
Myeloablative HCT is currently the only cure for SCD. It is recommended for patients younger than 17, those with severe symptoms of SCD unresponsive to hydroxyurea, or those with prior SCD-related organ damage (e.g., stroke chest syndrome, frequent painful episodes, multiple sites of osteonecrosis).
Unlike HCT for beta thalassemia major, in which the major issue is availability of a suitable donor, the current dilemma concerning HCT for SCD is patient selection and criteria for transplant. HCT is recommended for patients with severe symptoms of SCD that are unresponsive to treatment with transfusions and hydroxyurea if an HLA-matched sibling is available as a donor. The SCH-free survival is approximately 80-90% after HCTZ with a 7 to 10% mortality from HCTZ. Early HCT in young children with SCD may reduce SCD and HCT morbidity and mortality; however, since accurate predictors about the severity of SCD in children have not been identified, this approach is as yet undefined.
The newest investigational treatment for SCD was reported in NEJM (New England Journal of Medicine) this year. The patient is a 13-year-old French boy, treated at Necker Children’s Hospital in Paris. His bone marrow was removed and then altered in a laboratory to compensate for the DNA defect causing the disease. A virus with new DNA instructions was used to infect the bone marrow to correct the DNA defect. The bone marrow was then put back into the patient. The teen is now making normal blood 15 months later with no evidence of disease or pain or hospitalization. This treatment is currently only available in special cutting edge laboratories and hospitals. With time, this treatment may transform the lives of people with SCD.
What are possible options prior to having SCD and facing this dilemma?
Long a method in cultures and religions with arranged marriages, this necessitates testing an individual for a recessive disease prior to “mating or dating”. This approach has been used in religious groups, which employ a “matchmaker” to arrange a suitable match between couples as dictated by their parents. The “Matchmaker” will only “match” children who do not carry the same recessive genes for a serious disease such as cystic fibrosis, sickle cell disease, Tay Sachs disease and others.
But what if 2 adults find each other without a “matchmaker” and are aware that a serious recessive disease runs in their families such as SCD, and they have seriously affected and disabled relatives. They each underwent carrier screening and found out they are both SCD carriers. What are their options?
- Split up and find a partner who is not a carrier of SCD or affected.
- Hope for the best that they will be not have a child w/ SCD (25% chance) vs. a 25% unaffected with SCD or 50% chance of being a Sickle trait carrier like both parents.
- IVF with embryo biopsy prior to transfer and pregnancy of an embryo without SCD.
I have a couple in which she and her husband are both SC trait carriers and already experienced a pregnancy with SCD. They came to IRMS to select an embryo for transfer and hopefully have a pregnancy that was not affected with SCD. They did a cycle and have both unaffected and carrier embryos available for transfer.
IRMS has, since our inception in 1995, been the worldwide leader in the development and application of diagnostic genetic technology specifically designed to for human embryos. Many of the procedures that are currently used in all advanced IVF centers were developed or refined at IRMS. If you have questions regarding the risks of passing SCD or another genetic disorder on to your future children, please reach out and book a consultation. We can be reached at (973) 322–8286 or fill out our contact form. We look forward to helping you.