Spontaneous fertility in a male thalassemic patient after allogeneic hematopoietic cell transplantation

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Nicoletta Iacovidou
Maria Kollia
Emmeleia Nana
Theodora Boutsikou
Christos Savvidis
Antonis Kattamis
Dimitra Kyriakopoulou
Vassilis Ladis *
(*) Corresponding Author:
Vassilis Ladis | vassilisladis@gmail.com


Patients with thalassemia major who received allogeneic hematopoietic cell transplantation are at increased risk of gonadal insufficiency and reduced fertility due to the toxicity of both the transfusional iron overload and the gonadotoxic effects of drugs used in the conditioning regimen. We present a case of an ex-thalassemic patient with spontaneous recovery of spermatogenesis that fathered a healthy, term male neonate. Maternal hemoglobin electrophoresis was within normal limits. At the age of 9.5 years the patient underwent hematopoietic cell transplantation. The conditioning therapy included busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). No irradiation was administered. Thirty-two days after the hematopoietic cell transplantation the patient developed acute graft-versus-host disease needing long-term treatment with methylprednisolone, cyclosporine and immunoglobulin. Although consecutive semen analyses after the hematopoietic cell transplantation revealed azoospermia, the last semen analysis before conception, at the age of 33 years, was improved and normal follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (Te) levels were detected. The current pregnancy was the result of physical conception. In this case, it seems that thalassemia major along with the respective treatment prior to- and posthematopoietic cell transplantation did not irreparably impair spermatogenesis, probably due to the pre-pubertal time frame they were implemented.


对于接受异基因造血细胞移植的重型地中海贫血患者,由于输注性铁过载的毒性和预处理方案中所用药物性腺毒性作用这两方面的原因,都使其面临更大的性腺功能不全风险和更低的生育力。本文报道一例精子发生出现自然恢复的原重型地中海贫血患者,他成功孕育出一个健康的足月男婴。母体血红蛋白电泳在正常范围内。患者在9岁半时接受了造血细胞移植。预处理治疗包括白消安(16 mg/kg)和环磷酰胺(200 mg/kg)。未给予照射。造血细胞移植32天后,患者出现急性移植物抗宿主病,需要长期使用甲基强的松龙、环孢素和免疫球蛋白治疗。虽然造血细胞移植后连续的精液分析显示无精子症,但在33岁时受精前的最后一次精液分析有所改善,经检测发现卵泡刺激素(FSH)、黄体生成素(LH)和睾酮(Te)水平正常。目前的怀孕是自然受孕的结果。在这个病例中,看来重型地中海贫血以及造血细胞移植前后相应的治疗并没有对精子发生造成不可恢复的破坏,这可能是由于移植时处于青春发育期前时间段的原因。

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