Successful treatment of Griscelli syndrome with unrelated donor allogeneic hematopoietic stem cell transplantation

Abstract

Summary:Griscelli syndrome (GS) is a rare autosomal recessive disorder, characterized by pigmentary dilution of the skin and hair and in most patients by abnormal regulation of the immune system, which results in a syndrome of macrophage hyperactivation, known as hemophagocytic lymophohistiocytosis (HLH). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for genetically induced HLH. Few cases of successful HSCT from a compatible donor have been reported in children with GS. We describe the first patient with GS cured with an allograft from a compatible unrelated bone marrow donor. We used a novel preparative regimen consisting of busulfan, thiotepa and fludarabine. The demonstrated curative effect of HSCT from an unrelated donor in a patient with genetically determined HLH also supports the use of a systematic diagnostic approach in these patients, in order to identify those with a worse prognosis and needing an urgent allograft in a timely manner. Bone Marrow Transplantation (2002) 29, 995-998.

Hematopoietic SCT in children with Griscelli syndrome: a single-center experience

“…Only a few cases of successful aHSCT have been described previously. [9][10][11][12][13][14] Schmid et al 26 recently reported their experience with aHSCT for 10 patients with type 2 GS. At a medium follow-up of 3.4 years, the OS was 70%.…”

“…To date, few cases of aHSCT in patients with GS have been reported. [9][10][11][12][13][14] Materials and methods Table 1. The median age at diagnosis was 6.8 (range, 0-17.2) months.…”

Griscelli syndrome and electroencephalography pattern

“…Griscelli and Prunieras 1 , in the first description of the syndrome, did not described any neurologic manifestations. Latter, many authors reported the presence of seizures, intracranial hypertension, hemiparesis, facial palsy, hypotonia, psychomotor and language delay, progressive neurologic deterioration, cerebellar signs and spasticity [4][5][6][7][8][9][10][11][12] . According to Malhotra et al 3 severe neurologic abnormalities are common in GS type 1 and may be absent in GS type 2.…”

“…The physiopathology of GS is based on a limited transport of melanin taking to a melanossoma deposition in the melanocytes 4 . Many of these cases were found in multiple siblings and/or consanguineous parents, suggesting an autossomal recessive inheritance 5,6 . In 1997, Pastural et al 7 found a homozygous mutation of the gene encoding myosin VA protein (MYO5A) in a Turkish girl with Griscelli syndrome.…”

“…GS 2 represents patients with silvery gray hair, immunologic abnormalities and variable neurologic defects and is related to RAB27A gene. Finally, GS 3 presents as hypopigmentation in the hair and skin without another findings and is related to a mutation in the 2q37.3 chromossome [4][5][6][7] . The diagnosis is frequently made between 4 months and 7 years of age, with a 6-week-old patient being the youngest case reported 8 .…”