Reduced Intensity Conditioning Matched Unrelated Donor Allograft for Kostmann Syndrome.

Kostmann syndrome is a congenital disorder of myelopoeisis characterized by an absolute neutropaenia and severe bacterial infections. The introduction of G-CSF has dramatically changed the prognosis of these patients in recent years; though in G-CSF refractory patients, haemopoeitic stem cell transplant is still the only effective treatment. We describe the first case report of a patient who, unresponsive to escalating doses of G-CSF, underwent reduced intensity conditioning, Matched Unrelated Donor (MUD) allograft and has been cured from this condition. A male child presented shortly after birth with infection of the umbilicus. He developed repeated infections in the first six weeks of his life including pneumonia and scrotal abscess. Investigations at this stage included a bone marrow examination, which confirmed a diagnosis of severe congenital neutropaenia and he was started on treatment with G-CSF at 5μg/kg/day. Since diagnosis, he had numerous episodes of ear and skin infections and recurrent abscesses, most often with Methicillin resistant Staphylococcus aureus (MRSA) that required repeated hospitalisations. As the patient did not have a matched related donor, dose escalations were tried with G-CSF at 14-day intervals though he did not respond to doses up to 160μg/kg/day. At this stage, we had a child who was not responding to G-CSF injections, had several infections and was a carrier of MRSA and also Vancomycin Resistant Enterococci, who did not have a matched sibling donor. It was decided then to proceed with a MUD transplant with a non-myeloablative prepatory regimen. The pre transplant conditioning included fludarabine 30mg/m² from day −8 to day −5, CAMPATH-1H 0.2 mg/kg from day -6 to day −2 and thiotepa 250 mg/m² from day −4 to −2. Ciclosporin was started from day −1 and GCSF (Lenograstim) at 5μg/kg from day +7. A total of 10.4×10⁶ CD 34+ cells/kg recipient’s weight of stem cells was infused. The patient successfully engrafted with a neutrophil count greater than 0.5×10⁹/L on day 12 with an unsupported platelet count reaching above 50×10⁹/L on day 33. The post transplant period was complicated with grade II skin and gut GVH that responded well to increased doses of ciclosporin alone. Slight falls in neutrophil count were noted on days 28 and 113 after transplant, which resolved by adjusting ciclosporin dosage. He is now ten months post transplant and has not had any infections needing hospitalization and maintains his neutrophil count.

Conclusion

We have therefore demonstrated for the first time that reduced intensity conditioning transplant from a matched unrelated donor is a safe and effective treatment for uncomplicated Kostmann syndrome.