Allogeneic blood SCT for children with Hurler's syndrome: results from the German multicenter approach MPS-HCT 2005

Abstract

Hurler's syndrome is an inborn error of mucopolysaccharide metabolism leading to premature death in childhood. Allogeneic hematopoietic SCT can achieve long-term survival by correcting the enzymatic deficiency. In an attempt to improve long-term engraftment and to reduce regimen-related toxicity (RRT), a prospective multicenter approach was initiated in Germany using a fludarabinebased radiation-free preparative regimen. Between 2001 and 2008, 12 children were enrolled. Median age at SCT was 14 months (range, 4-31 months). The conditioning regimen contained fludarabine, BU, melphalan and antithymocyte globulin. CD34 positively selected PBSC were used in 10 children with a matched unrelated donor. Median cell dose was 24.6 Â 10 6 CD34 þ cells per kg (range 10.0-54.8). Two children with a matched sibling donor received non-manipulated BM. Donor lymphocyte infusions were given in 6/12 children for mixed hematopoietic chimerism. At a median follow-up of 29 months (range 2-85 months), all children engrafted and have either stabilized or improved neurological function. In total, 12/12 patients showed donor-derived engraftment with 9/12 having full and 3/12 having mixed hematopoiesis. One developed acute GVHD Xgrade II. RRT Xgrade II was observed in two patients.

Unrelated CD3/CD19-Depleted Peripheral Stem Cell Transplantation for Hurler Syndrome

“…However, busulfan in combination with cyclophosphamide may be associated with veno-occlusive disease, pulmonary and cardiac toxicity. The German multicenter approach MPS-HCT 2005 successfully used a preparative regimen consisting of busulfan/fludarabine/melphalan/ATG [13]. The EBMT currently recommends the combination of busulfan (in weight-based dosing with therapeutic drug monitoring) with fludarabine.…”

“…Patients with MPS1-H undergoing HSCT are at risk of two main complications, namely, graft failure and regimen-related toxicity [12,13], that determine the choice of donor, stem cell source, and preparatory regimen.…”

“…The German multicenter approach MPS-HCT 2005 used CD34 positively selected peripheral stem cell grafts from MUD in 10/12 children with megadoses of stem cells. All patients were alive, engrafted, and without neurological deterioration; 6/12 children received donor lymphocyte infusions (DLI) for mixed hematopoietic chimerism; only one patient developed acute GVHD ≥grade II [12,13].…”

Hematopoietic stem cell transplantation in patients with Hurler syndrome – myeloablative conditioning efficiency

“…В последние годы, не-смотря на успехи применения режимов со сниженной токсичностью, прочное место занимают режимы пол-ной интенсивности. Учитывая модификацию данных режимов (внедрение треосульфана) и улучшение каче-ства сопроводительной терапии, а также ранней диаг-ностики самого заболевания, удалось улучшить резуль-таты терапии [10]. Кроме того, в большинстве протоколов циклофосфамид заменен на флударабин с целью снижения токсичности, а для дополнительной миелоаблации (учитывая высокий потенциал отторже-ния) в терапию был добавлен мелфалан.…”

“…В нашем исследовании показана возможность при-менения неманипулированного трансплантата с мень-шей вероятностью отторжения по сравнению с резуль-татами ТГСК с CD34-селекцией [10]. Применение нативного трансплантата показано в рекомендациях Европейской группы по трансплантации крови и кост-ного мозга (EBMT).…”