Successful management of mixed chimerism after bone marrow transplant in beta-thalassemia major

2016 ◽  
Vol 91 (9) ◽  
pp. E357-E358
Author(s):  
Gabriele Kropshofer ◽  
Sieghart Sopper ◽  
Michael Steurer ◽  
Wolfgang Schwinger ◽  
Roman Crazzolara
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Thalassemia Major ◽  
Marrow Transplant ◽  
Mixed Chimerism ◽  
Beta Thalassemia ◽  
Successful Management ◽  
Beta Thalassemia Major

COMBINED UMBILICAL CORD BLOOD AND BONE MARROW TRANSPLANT ATION IN THE TREATMENT OF BETA-THALASSEMIA MAJOR

2000 ◽  
Vol 17 (4) ◽  
pp. 307-314 ◽  
Author(s):  
Evgenios Goussetis ◽  
Julie Peristeri ◽  
Vasiliki Kitra ◽  
Antonios Kattamis ◽  
Demetrios Petropoulos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Bone Marrow Transplant ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Thalassemia Major ◽  
Marrow Transplant ◽  
Beta Thalassemia ◽  
Beta Thalassemia Major

Pharmacogenetics of Cyclophosphamide in Patients with Beta Thalassemia Major Undergoing Bone Marrow Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 99-99
Author(s):  
Balasubramanian Poonkuzhali ◽  
Desire Salamun ◽  
Ramachandran V. Shaji ◽  
Biju George ◽  
Vikram Mathews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Individual Variation ◽  
Marrow Transplantation ◽  
Systemic Exposure ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Mutant Genotype ◽  
Beta Thalassemia Major ◽  
Homozygous Mutant

Abstract Cyclophosphamide (Cy) is commonly used in conditioning therapy for bone marrow transplantation (BMT). The conversion of Cy to its first active metabolite 4-hydroxy cyclophosphamide (4-HCy) is mediated by several enzymes of the cytochrome P450 (CYP450) family [CYP2B6, 2C9, 2C19 and 3A4]. Since the pharmacokinetics (PK) of 4-HCy is formation rate limited, the AUC ratio of 4-HCy/Cy reflects better the degree of systemic exposure to 4-HCy. The PK of Cy and HCy exhibits up to 20 fold inter-individual variation in patients during conditioning. To understand the mechanisms underlying the variation in Cy metabolism, we analyzed the PK of Cy and 4-HCy in 40 consecutive patients with beta thalassemia major undergoing BMT and correlated them with the common polymorphisms of CYP450 2B6, 2C9 and 2C19 genes and the pre transplant hepatic status (Lucarelli class) of the patient. All patients received Cy at a dose of 50mg/kg as one-hour intravenous infusion for 4 days (day -5 to -2) after 4 days of busulfan (day-9 to -6). Levels of Cy and 4-HCy were measured using high performance liquid chromatography. Genotyping for CYP2B6 G516T, CYP2C9 *2, *3 and CYP2C19*2 and *3 were done using PCR-RFLP methods. There was a 4–20 fold inter-patient variation in the PK of Cy and 4-HCy. Mean AUC of Cy was 2288±1169 mg* h/ml, (range: 674–5126), while that of AUC of 4-HCy was 5.67±2.52 mg* h/ml (range: 0.817–11.17). Patients with wild type CYP2B6 G/G genotype had significantly higher Cy 4-hydroxylation than those with the homozygous mutant genotype (T/T). CYP4502B6, 2C9, 2C19 genotypes and ratio of AUC 4HCy/AUC Cy CYP2B6 G/G (n=15) G/T (n=8) T/T (n=16) t-test p value 0.0033±0.0014 0.003±0.0013 0.0023±0.0011 0.03 (G/G vs. T/T) CYP2C9 *1/*1 (n=25) *1/*2 (n=3) *1/*3 (n=9) *2/*3 (n=2) *3/*3 (n=1) 0.003±0.0016 0.0037±0.0009 0.0023±0.0011 0.0014, 0.0015 0.0073 0.076 (*1/*2 vs. *1/*3) CYP2C19 *1/*1 (n=26) *1/*2 (n=10) *2/*2 (n=3) 0.0026±0.001 0.0036±0.0012 0.0029±0.0013 0.016 (1/1 vs. 1/2) One patient with homozygous mutant genotype CYP 2C9 3/3 showed 2.6 fold higher Cy 4-hydroxylation (0.0073 vs. 0.0026), while two patients with CYP2C9 2/3 genotype had 2 fold lower than the mean of the ratio for all 2C9 genotypes. Patients with CYP2C19 1/2 genotype showed significantly higher ratio than those with CYP2C19 1/1 genotype. No association was found between patients’ pre- transplant liver status (Lucarelli class) and Cy 4-hydroxylation. We conclude that 4-hydroxylation of Cy is significantly influenced by CYP2B6, 2C9 and 2C19 genotypes. This could explain the wide inter individual variation in Cy PK which should be correlated with toxicity and outcome of BMT.

Gonadal Function In Patients with Beta-Thalassemia Major Following Bone Marrow Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4105-4105
Author(s):  
Khalil Al Farsi ◽  
Murtadha K. Al-Khabori ◽  
Fehmida Zia ◽  
Moez Abdul-Rahim ◽  
Yusra Al-Habsi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Total Dose ◽  
Thalassemia Major ◽  
Inhibin B ◽  
Beta Thalassemia ◽  
Gonadal Function ◽  
Beta Thalassemia Major ◽  
Male Patients

Abstract Abstract 4105 Introduction: Conditioning chemotherapy prior to allogeneic bone marrow transplantation (BMT) can induce impairment in gonadal function. Patients with beta-thalassemia major generally undergo BMT at a young age and long-term data on its effects on gonadal function in this patient population are limited. Aims and objectives: To address the effect of BMT on gonadal function in long term survivors with beta-thalassemia major following successful BMT. Materials and methods: The hormonal profiles of gonadotrophins (LH and FSH), sex hormones (total and free testosterone in males, and 17 beta-estradiol in females) and inhibin B were assayed yearly after BMT. We analyzed data on patients who underwent BMT between January 1996 and June 2009 in whom the pubertal process should have started. Results: A total of 84 patients received BMT for thalassemia major; 51 (20 females and 31 males) have reached the age of puberty at the time of this analysis. Median age at transplant was 10 years (range: 3 – 17). With a median follow-up of 8 years (range: 2–15), the median age at last follow-up was 18 years (range: 13 – 26). All transplants were from matched sibling donors. Conditioning was myeloablative and consisted of: Busulfan, total dose of 600mg/m2 and Cyclophosphamide, total dose 200mg/kg (BuCy) before January 2005 and Busulfan, total dose 520mg/m2, Fludarabine, total dose 180mg/m2 and ATG, total dose 40mg/kg (BuFluATG) from January 2005 onwards. The impact of BMT appears to be different in the two sexes. 18 of 20 (80%) female patients had evidence of primary ovarian failure. Leydig cell failure was seen in only two male patients. However, injury to the germinal epithelium (as shown by low inhibin B levels which is predictive of oligo- or azoospermia) was seen in 22 of 31 (70%) male patients. A correlation was not found between the low inhibin B levels and age at BMT or type of conditioning regimen. Conclusion: Our data confirm that gonads in male and female thalassemic patients are affected by the cytotoxic effects of the preparative regimens of BMT, albeit at different levels. These findings emphasize the need for vigilant long term follow up of thalassemic patients post-BMT so that those requiring hormone replacement therapy can be identified and treated early. These findings are also important for pre- and post-BMT counseling. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Allogenic Bone Marrow Transplant for Thalassemia Major—a Single Center Experience From India

2018 ◽  
Vol 24 (3) ◽  
pp. S422
Author(s):  
Dharma Choudhary ◽  
Divya Doval ◽  
Sanjeev Sharma ◽  
Vipin Khandelwal ◽  
Rasika Setia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Thalassemia Major ◽  
Marrow Transplant ◽  
Single Center ◽  
Allogenic Bone ◽  
Allogenic Bone Marrow ◽  
Single Center Experience

scholarly journals Allogeneic bone marrow transplant in the absence of cytoreductive conditioning rescues mice with β-thalassemia major

2017 ◽  
Vol 1 (25) ◽  
pp. 2421-2432 ◽  
Author(s):  
Yongliang Huo ◽  
Jonathan R. Lockhart ◽  
Shanrun Liu ◽  
Suean Fontenard ◽  
Mike Berlett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Bone Marrow Transplant ◽  
Marrow Transplantation ◽  
Globin Gene ◽  
Thalassemia Major ◽  
Marrow Transplant ◽  
Allogeneic Bone ◽  
Key Points ◽  
Gene Switch

Key Points After completion of the fetal-to-adult globin gene switch, humanized β-thalassemia major mice are transfusion dependent. Perinatal humanized β-thalassemia major mice are rescued by bone marrow transplantation in the absence of cytoreductive conditioning.

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