Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong: prognostic factors and outcome

Li, Chi Kong; Shing, Matthew Ming-Kong; Chik, Ki Wai; Lee, Vickie; Leung, Ting Fan; Cheung, Albert Y.; Yuen, Man-Fung

doi:10.1038/sj.bmt.1703340

Cited by 34 publications

(30 citation statements)

References 20 publications

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“…The details on BMT outcome and occurrence of endocrine complications for the transplanted patients have been described previously. 13,14 Briefly, BMT conditioning most commonly used included busulphan (16 mg/kg), cyclophosphamide (150-200 mg/kg) and antithymocyte globulin (90 mg/kg). GVHD prophylaxis consisted of methotrexate (15 mg/m 2 on day 1 and 10 mg/m 2 on days 3, 6 and 11) and cyclosporin A (1.5 mg/kg every 12-hourly from day À1).…”

Section: Patient Assessmentmentioning

confidence: 99%

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation

Leung

Hung

Lam

et al. 2005

Bone Marrow Transplant

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Summary:Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.771.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score oÀ2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (b ¼ À0.463; P ¼ 0.006) was predictive of spine BMD, whereas age (b ¼ À0.843; P ¼ 0.007) and urine DPD (b ¼ À0.439; P ¼ 0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (b ¼ 0.450; P ¼ 0.009) and serum bone-specific ALP (b ¼ À0.495; P ¼ 0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P ¼ 0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) lg/l and 68.9 (40.3) lg/l, respectively (P ¼ 0.037).In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients. Osteoporosis and osteopenia are major long-term complications of thalassaemia major (TM). A number of studies have been performed using dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) in patients with transfusion-dependent thalassaemia. [1][2][3][4][5] The prevalence of reduced BMD varied, but Jensen et al 1 reported that half of their 82 patients had severely low BMD whereas the other 45% had low bone mass. Angastiniotis et al 5 showed that patients with thalassaemia intermedia were not spared, and 75% of them had BMD below À2 s.d. even with transfusion started only later in life. BMD correlates with the risk of fractures. DEXA is currently the most reliable and widely used method for measuring BMD, and this technique assesses bone mass classically at the lumbar spine and proximal femur. 6,7 There are well-established normal standards for DEXA measurements for Caucasian and Chinese children. [6][7][8] Both genetic and acquired factors may contribute to the reduction in BMD in TM patients. Concerning the genetic regulation, Sp1 polymorphism in the gene encoding type 1 collagen (major) protein (COLIA1) was found to be associated with the severity of osteopenia at spine and hip in male thalassaemic patients, and the same genetic factor also predicted treatment failure to bisphosphonate. 3 Acquired factors contributing to skeletal morbidity include endocrinopathy, direct iron-induced toxicity, bone marrow expansion and the use of iron-chelating therapy. [9][10][11][12] However, the effects of BMT, being the only curative treatment for TM, on BMD measurements have not been reported. We hypothesise that the diminished BMD seen in TM patients may improve wh...

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Section: Patient Assessmentmentioning

confidence: 99%

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation

Leung

Hung

Lam

et al. 2005

Bone Marrow Transplant

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“…Currently, the only cure for thalassemia is allogeneic bone marrow transplantation which corrects the genetic defect in the hematopoietic system 2 by the use of allogeneic stem cells, the origin of which must be immunologically acceptable. 3,4 Patients with thalassemia can be categorized into 3 classes of risk for marrow transplantation, 5,6 and the category of greatest risk is class 3. 7 The outcome of bone marrow transplantation was studied for 122 consecutive patients with class 3 thalassemia aged younger than 17 years prepared with a regimen of busulfan (BU) 14 mg/kg followed by cyclophosphamide (CY) 120 or 160 mg/kg.…”

Section: Introductionmentioning

confidence: 99%

New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years

Sodani¹,

Gaziev²,

Polchi³

et al. 2004

Blood

184

136

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When prepared for transplantation with busulfan (BU) 14 mg/kg and cyclophosphamide (CY) 120 to 160 mg/kg, patients with thalassemia in risk class 3, aged younger than 17 years, who receive transplants from HLA-identical donors, had a 30% incidence of transplant rejection with recurrence of thalassemia. This, relatively poor, outcome was ascribed to insufficient immune suppression or to inadequate eradication of the thalassemic marrow, or both. In an attempt to enhance both immune suppression and eradication of the thalassemic clones, hydroxyurea, azathioprine, and fludarabine were added to the BU and CY. This regimen, called protocol 26, was applied to 33 consecutive patients with class 3 thalassemia aged younger than 17 years and was well tolerated with 93% survival. The incidence of recurrent thalassemia after the transplantation decreased from 30%

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“…Similar findings have recently been reported in the Chinese population in Hong Kong [2]. The conditioning regimen was modified in accordance to the experiences of the Malaysian and Thai groups, who had performed large numbers of matched sibling transplants (verbal communication).…”

Section: Discussionmentioning

confidence: 58%

Unrelated peripheral blood and cord blood hematopoietic stem cell transplants for thalassemia major

et al. 2004

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Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment available for thalassemia major. While sibling donors are usually used, unrelated bone marrow transplants have also recently been found to be successful. In this report of two patients, we show that, besides using unrelated bone marrow, peripheral blood stem cell and cord blood transplantations from unrelated donors are viable options. We believe a significant contributory factor in both our cases was the large cell dose used.

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Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong: prognostic factors and outcome

Cited by 34 publications

References 20 publications

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation

New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years

Unrelated peripheral blood and cord blood hematopoietic stem cell transplants for thalassemia major

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