Bilateral basal ganglial necrosis after allogeneic bone marrow transplantation in a child with Kostmann syndrome

Abstract

Summary:A 6-year-old girl underwent allogeneic BMT from a matched sibling donor for the treatment of Kostmann syndrome. She suddenly became drowsy on day 30 after BMT, and lost consciousness 2 days later. Cranial CT scan showed symmetrical lesions suggesting bilateral necrosis in the basal ganglia. Clinical and laboratory investigations failed to reveal any evidence of neurometabolic disease. Keywords: bilateral basal ganglial necrosis; allogeneic BMT; Kostmann syndrome Acute encephalopathy with symmetrical lesions in the basal ganglia is a rare neurological disease. Generally either a preceding illness or underlying metabolic disease exists in most reported cases. Bilateral basal ganglial necrosis, especially infantile striatal necrosis has been reported to occur often after a non-specific febrile upper respiratory infection. We describe a child who experienced this disease after allogeneic BMT without any definite preceding episodes or metabolic disorders, and presently suffers from severe neurological sequelae. Case reportA neurologically normal 6-year-old girl underwent allogeneic BMT for Kostmann syndrome from an HLA-identical sibling donor. Conditioning consisted of busulphan 35 mg/m 2 p.o. four times daily from day −9 to day −6, ATG 2.5 mg/kg i.v. daily and cyclophosphamide 50 mg/kg i.v. daily from day −5 to day −2. She developed a high grade fever and generalized tonic clonic seizure for a few minutes during the first administration of ATG on day −5. No neurological sequelae could be found after the seizure resolved. She had no past history of febrile convulsions or epilepsy. Initially phenytoin 10 mg/kg i.v. was given twice Correspondence: Dr J Okamura, Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan Received 26 May 1998; accepted 3 October 1998 daily for seizure prophylaxis from day −9. Hydrocortisone 125 mg i.v. was added as an antipyretic and no seizure occurred thereafter. Cyclosporin A was used for graftversus-host disease prophylaxis.Engraftment was confirmed on day 12 after BMT when the neutrophil count reached 500/ l. The patient experienced asymptomatic mild hyponatremia which started on day 11 and lasted for 30 days. The serum sodium concentration varied between 121 to 133 milliequivalents per liter (mEq/l). The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was thus suspected because her urinary osmolarity and serum antidiuretic hormone levels were normal although the plasma osmolarity was mildly decreased below the normal limits. Hyponatremia resolved on day 41 with water restriction and a half correction of sodium. The patient suddenly became drowsy on day 30 and lost consciousness 2 days later. No preceding episodes including fever, vomiting, or seizures were observed. A neurological examination on day 32 showed a comatous state of consciousness without any response to painful stimulation except for slight movement of the left upper limb. The patient remained in the supine position, and showed an asymme...

Hematopoietic stem cell transplantation for severe congenital neutropenia

“…There are currently 18 published reports of HCT in patients with SCN for a total of 65 patients transplanted without malignant transformation (Tables 1 and 2)[8 ⍰ , 40, 41 ⍰ , 42 ⍰ , 43–51, 52 ⍰ , 53, 54] and 18 patients transplanted with development of MDS or leukemia (Table 3)[8 ⍰ , 41 ⍰ , 43, 55, 56]. Indications for proceeding to transplant have included poor response to G-CSF (most common), development of G-CSFR mutation(s), inability to tolerate G-CSF injections, infection unresponsive to GCSF and anti-microbials, development of cytogenetic changes consistent with MDS, and morphologic evidence of MDS or leukemia.…”

Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: An analysis of 18 Japanese cases

“…However, it remains difficult to recommend transplantation to patients with SCN who respond well to r‐HuG‐CSF treatment and show no evidence of impending malignant transformation, even if the patient has an HLA‐identical sibling donor (7). A high rejection rate was observed in our study, with four of the 18 patients developing post‐transplant complications, including renal failure (n = 1), chronic GVHD (n = 2), and bilateral basal ganglia necrosis (n = 1) (28) after the first transplantation. However, some results of this study might have been affected by the long study duration.…”

Congenital bone marrow failure syndromes

“…Only two case reports of BMT in KS have been published, although BMT should theoretically be curative and free of the potential toxicities of long‐term cytokine treatment (Zintl et al , 1991). In one case, BMT was associated with bilateral necrosis of the basal ganglia (Suga et al , 1999).…”