HSCT in children with sickle cell Disease

the Majority in children with an HLA matchel sibling donor HSCT is currently the only curative option for SCD) To Date , about 1200 Transplants has been reported in the European and us transplant registries the Majority in children with an HLA matchel sibling donor Using MSD and myebablative regime ,the rate for mortality ,rejection and cure are 5% , 5% and 90% Respectively After HSCT VOCs are abolished , CNS diesase stabilized (but )usually not improved . TCD normalized and QOL is much improved

Long Term complication of HSCT in children include loss of fertility due to primary gonadal failure / skeletal complication (osteoporosis) Very Small increase in the risk of malignant disease Long term outcome is generally much in favour of BMT compared to standard care

Current indication for matched sibling HSCT in children Recurrent VOC complication (acute pain or ACS) not responding to Hydroxyurea Past History of ischemic stroke or sever cerebral vasculopathy Abnormal TCD flow with evidence of ischemic cerebral damage Sever avascular necrosis Multiple red cell alloantibody restricting availability of blood for transfusion

Nephropathy Problem relating to future care(e.g likely return to home country where health care services are inadequate) Any child with Hb ss irrespective of severity , if an HLA compatible sibling donor is available.

Risk and Benefits Most specialist begin the dicussion about possible HSCT with parents early during the first year Of life And then at the appropriate occasion later childhood

The first outcome of this discussion is an agreement for compatibility testing of sibling (if available) If a donor is identified a fuller Discussion and assessment is initiated , together With referral to a specialist transplant unit.

The decision to go ahead can be very difficult for parents because it is difficult to predict long-term prognosis for young child who may not be particularly severely affected at the time of the discussion

The transplant procedure HSCT in SCD should only be performed in centers experienced in transplanting hemoglobinopathy patients Acute GVHD appears to be increased with use of donor peripheral blood and bone marrow is advised as a source of donor stem cells

There is a higher risk of delayed engraftment with umbilical cord Blood transplants. Cord blood is generally not recommended as the sole source of stem cell ,at least in older children.

There are specific requirements for conditioning in SCD transplants including pre- transplant hypertransfusion and marrow suppression with hydorxyurea Granulocyte colony stimulating Factor (GCSF)is not used for stimulation of neutrophile Recovery because of the risk of precpitating a severe VOC crisis.

In addition to higher risk of acute neurological events in the presence of cerebral vasculopathy there is also a significant increased risk of PRES

Alternative Donor 10-15% of patients have an HLA mathed sibling Donor Alternative include MUD/or haplo identical (half matched) familiy donors In general mortality and morbidity are increased with the use of alternative donors Considered in patients with sever complication of SCD

They should only be undertaken as part of a research practice . The graft failure rate is over 50% which is unacceptable

HSCT in adults The outcomes for adult using HLA.matched sibling donors are poorer than In children A recent single – center study using non-myeloablative conditioning and a novel immunosuppressive regime has reported long term stable mixed donor- recipient chimerism (donor and host cells co-existing )in 9 of 10 patients

Indication for transplant included irreversible and end-organ damage stroke or other significant CNS events Interestingly some of patient had severe acute and chronic pain which gradually resolved enabling withdrawal of chronic opioid medication Unfortunately the requirement for an HLA matched sibling donor still restricts this approach to a small minority of adult patients.

Umbilical cord blood HSCT and storage of cord blood UCB from babies who are HLA matched can be stored and used as a source of HSC This scenario would usually occur after PND has confirmed that the sibling is unaffected and subsequent HLA typing of the CVS sample has confirmed HLA matching . Storage without PND cord blood banking would probably not be funded by health authorities.