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Successful treatment of a patient with Klinefelter's syndrome complicated by mediastinal germ cell tumor and AML(M7)

Bone Marrow Transplantation volume 41, pages 907–908 (2008)Cite this article

The association of mediastinal germ cell tumors (GCTs) and hematological malignancy has been documented for more than 20 years.1, 2 This rare association is known to be extremely refractory to modern therapy. Here we report the successful treatment of a boy with Klinefelter's syndrome complicated by this disease.

Cases of mediastinal GCT associated with hematological abnormalities have been reported since the 1980s. In 1990, Nichols et al.4 described 16 cases of GCT, including two cases, which seemed to have Klinefelter's syndrome. All patients were relatively young males and had nonseminomatous mediastinal germ cell tumors. AML (M7) and malignant histiocytosis were the most common hematological abnormalities. In one patient, i(12p) isochromosome was identified in both the GCT and leukemic blasts. Woodruff et al.5 also identified i(12p) in both the mediastinal GCT and associated hematologic malignancy. Orazi et al.6 reported hematopoietic precursors within the mediastinal GCT in patients with this association. With these observations, the hypothesis that the leukemic clone originates from GCTs has been suggested. Although histological examination did not demonstrate any hematopoiesis in GCT in our patient, chromosome analysis showed marked similarities between GCT cells and leukemic blasts (Table 1), which supports this hypothesis. Considering previous findings that patients with this syndrome have an extremely poor prognosis due to leukemia, we administered chemotherapy before surgical removal of the mediastinal cell tumor. Some reports argue against intensive consolidation therapy for AML.7, 8 However, in view of the fact that current protocols of major clinical trials for childhood AML contain consolidation therapy, and that four courses of bleomycin, etoposide and cisplatin are the standard therapy for extragonadal germ cell tumors,9 we concluded that AML99, standard treatment for childhood AML in Japan, which involved the use of cisplatin, would be a reasonable combination. With this therapy, our patient achieved CR and stabilization of mediastinal GCT. The reports that allogeneic HSCT for childhood AML with a poor prognosis can be a powerful therapeutic modality10, 11 and the efficacy of CBT for childhood AML in the first CR in Japan is as good as unrelated BM transplantation convinced us to undertake CBT using well-matched cord blood. Also, importantly, our patient did not experience severe GvHD, making surgery uncomplicated.

Table 1 Chromosomal analysis of germ cell tumor (GCT) and M7
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  1. Department of Pediatrics, Kyoto University, Kyoto, Japan

    H Hiramatsu, T Morishima, H Nakanishi, Y Mizushima, M Miyazaki, H Matsubara, M Kobayashi, T Nakahata & S Adachi

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  1. H Hiramatsu
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Hiramatsu, H., Morishima, T., Nakanishi, H. et al. Successful treatment of a patient with Klinefelter's syndrome complicated by mediastinal germ cell tumor and AML(M7). Bone Marrow Transplant 41, 907–908 (2008). https://doi.org/10.1038/sj.bmt.1705991

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