Hematopoietic cell transplantation for a child with OSTM1 osteopetrosis

Overholt, Kathleen M.; Rose, Melissa J.; Joshi, Sarita; Herman, Gail E.; Bajwa, Rajinder; Abu‐Arja, Rolla; Rangarajan, Hemalatha G.; Horwitz, Edwin M.

doi:10.1182/bloodadvances.2016002345

Cited by 15 publications

(21 citation statements)

References 16 publications

(29 reference statements)

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“…In fact, based on the implication of Ostm1 in neuronal homeostasis, curative treatment of OSTM1 patients is still challenging and consensus guidelines are being established [ 110 ]. Despite successful HSCT, neuronal pathology progresses in some OSTM1 patients [ 111 ]. However, the possible use of less invasive monocytic transfusions can give promise of less painful, more humane, and versatile therapies for OSTM1 patients.…”

Section: Ostm1 and Human Osteopetrotic Patientsmentioning

confidence: 99%

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

Vacher

Bruccoleri

Pata

2020

IJMS

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The maintenance of bone mass is a dynamic process that requires a strict balance between bone formation and resorption. Bone formation is controlled by osteoblasts, while osteoclasts are responsible for resorption of the bone matrix. The opposite functions of these cell types have to be tightly regulated not only during normal bone development, but also during adult life, to maintain serum calcium homeostasis and sustain bone integrity to prevent bone fractures. Disruption of the control of bone synthesis or resorption can lead to an over accumulation of bone tissue in osteopetrosis or conversely to a net depletion of the bone mass in osteoporosis. Moreover, high levels of bone resorption with focal bone formation can cause Paget’s disease. Here, we summarize the steps toward isolation and characterization of the osteopetrosis associated trans-membrane protein 1 (Ostm1) gene and protein, essential for proper osteoclast maturation, and responsible when mutated for the most severe form of osteopetrosis in mice and humans.

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Section: Ostm1 and Human Osteopetrotic Patientsmentioning

confidence: 99%

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

Vacher

Bruccoleri

Pata

2020

IJMS

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“…However, this remains controversial. According to a study by Overholt et al (20), early HSCT in patients without clinical or global neurological signs does not prevent the onset or progression of neurological deterioration. Recently, HSCT for AROP with a reduced-intensity conditioning regimen was proven to be safe and effective, providing us with the ability to performed HSCT on young patients with significant comorbidities soon after diagnosis, with a lower risk of severe side effects (21).…”

Section: Discussionmentioning

confidence: 99%

Successful total hip arthroplasty for autosomal dominant osteopetrosis complicated by hip osteoarthritis: A case report and review of the literature

et al. 2020

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Osteopetrosis is a rare congenital bone disorder, characterized by systemic osteosclerosis due to a deficiency of or functional defect in osteoclasts. Autosomal dominant osteopetrosis (ADOP) is the most common form with a late onset, a stable condition, relatively few symptoms and a good prognosis. Few studies to date have reported successful total hip arthroplasty (THA) in patients with ADOP and its operative difficulties. We herein describe a case of left hip osteoarthritis in a patient with OP via THA in order to share our experience during the treatment process. The patient was a 52-years-old female with osteopetrosis who was referred to our department due to a history of left hip pain with activity limitation for 20 years. The patient reported no history of fracture or family history. The patient underwent THA in the left hip. At the 6-month, 1-and 2-year follow-up, the components were in a good position and the patient remained asymptomatic and pain-free. Therefore, THA may be a feasible treatment option when patients with ADOP suffer from painful hip osteoarthritis.

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“…Вместе с тем ранняя диагностика значительно улучшает результаты лечения и может предотвратить инвалидизацию пациентов. При отсутствии лечения заболевание приводит к летальному исходу в течение первых 10 лет жизни ребенка, и только 30% больных переживают 6-летний возраст [9].…”

Section: Practice Of Allogeneic Hematopoietic Stem Cell Transplantatiunclassified

“…В посттрансплантационном периоде поражение костей претерпевает обратное развитие: восстанавливается рост и ремоделирование костей, происходит редукция экстрамедуллярных очагов кроветворения. Однако при атрофическом поражении черепно-мозговых нервов или патологии ЦНС компенсации утраченных функций не происходит [9]. В случае развития первичной нейропатической формы заболевание имеет неблагоприятный прогноз -прогрессирование симптоматики приводит к смерти большинства пациентов в возрасте до 2 лет.…”

Section: Practice Of Allogeneic Hematopoietic Stem Cell Transplantatiunclassified

“…Учитывая успешный опыт трансплантации с достижением перекрестной коррекции патологического процесса в ЦНС при мукополисахаридозе I типа (синдром Гурлер), проводились попытки трансплантации у пациентов с нейропатической формой остеопетроза. Трансплантацию выполняли у пациентов первых месяцев жизни -носителей транслокаций CLCN7, OSTM1 -при условии отсутствия поражения головного мозга к моменту трансплантации [9,23]. При использовании как бусульфан-, так и треосульфан-аблативного режима кондиционирования не было получено «неврологического приживления» и заместительного эффекта трансплантата у пациентов с первичной нейропатической формой MIOP.…”

Section: Practice Of Allogeneic Hematopoietic Stem Cell Transplantatiunclassified

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Practice of allogeneic hematopoietic stem cell transplantation for infantile autosomal recessive osteopetrosis

Буря¹,

Киргизов²,

Пристанскова³

et al. 2019

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Generalized osteopetrosis is a rare hereditary disease characterized by impairment of skeleton bones formation, bone marrow dysfunction, neurologic deficiency and blindness. The main treatment for osteopetrosis is an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To review and analyze experience of Department of bone marrow transplantation of RDKB (BMT RDKB) of allo-HSCT for patients with autosomal recessive generalized osteopetrosis; to evaluate tolerability and efficacy of the conditioning regiment administered. Between 2010 to 2018 years, 7 patients (2-male, 5-female) with autosomal recessive generalized osteopetrosis underwent allo-HSCT in tDepartment of bone marrow transplantation of RDKB. Median age at the moment of HSCT was 5,5 years (1–11 years). Before the transplantation myeloablative conditioning regimen was used: treosulfan, fludarabine and melphalan for 5 patients, treosulfan, fludarabine and thiotepa for 1 patient and treosulfan with fludarabine for 1 patient. In case of unrelated allo-HSCT antithymocyte globulin was added to the conditioning regimen. Bone marrow from matched (HLA- 10/10) unrelated donor was used for 4 patients, peripheral blood stem cells from matched unrelated donor was used for 1 patient, two grafts of unrelated umbilical cord blood (HLA 8/10 and 9/10) for 1 patient and peripheral blood stem cells from matched (HLA 10/10) from related donor – for 1 patient. For “graft-versus-host” disease (GVHD) prophylaxis either cyclosporine A/tacrolimus and methotrexate/ mofetil mycophenolate was used. White blood cell recovery had been achieved for 6 from 7 patients on +13 to +22 day (median +17 day). Quick autoreconstitution of hemopoesis was observed for the recipient of umbilical cord blood who got one myeloablative drug. The following early post transplantation complications were registered: oropharyngeal mucositis up to II degree in 6 patients, neutropenic enterocolitis up to II degree in 4 patients, up to III degree in 3 patients, sepsis in 3 patients. The GVHD symptoms occurred in 2 cases: skin form of II degree in one patient and skin form of II degree and intestinal form of IV degree in another patient. One patient with neurodegenerative form of osteopetrosis died with increase of hypertensive-hydrocephalus syndrome, cerebral edema with downward cerebellar herniation. During 5-6 months after allo-HSCT the 5 successfully transplanted patients experienced poor graft function but then reduction of extramedullary hemopoesis occurred and full engraftment was achieved. Hypercalcemia was reported in 2–5 months after allo-HSCT and was treated by administration of bisphosphonates. Visual impairment persisted after allo-HSCT. After 4–6 months after transplantation axis skeleton growth occurred for all 5 successfully transplanted patients, skull deformation reduced and no new zones of nerve’s compression were observed. No patients had any developmental delays after the treatment. Allo-HSCT is an effective systemic treatment of autosomal recessive generalized osteopetrosis. However because serious neurodegenerative condition cannot be reversed by allo-HSCT, such treatment may not be recommended for patients with heavy CNS impairment. Myeloablative conditioning regimen with two alkylating agents provides allogeneic reconstitution of hemopoesis. In post transplantation period, measures for hypercalcemia control are necessary. Early diagnostic of autosomal recessive generalized osteopetrosis can help to evaluate feasibility of allo-HSCT and to start treatment on time thus provide chance for long-term rehabilitation and prevention of serious disability. The study was approved by the Independent Ethics Committee of Russian Children's Clinical Hospital.

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Hematopoietic cell transplantation for a child with OSTM1 osteopetrosis

Abstract: Key Points HCT prior to onset of neurologic symptoms in children with OSTM1 osteopetrosis does not halt neurologic progression.

Cited by 15 publications

References 16 publications

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

Successful total hip arthroplasty for autosomal dominant osteopetrosis complicated by hip osteoarthritis: A case report and review of the literature

Practice of allogeneic hematopoietic stem cell transplantation for infantile autosomal recessive osteopetrosis

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