Case: Treatments for Germ Cell Tumors Could Lead to CML

A case series of three individuals suggests that there may be a causal relationship between chemotherapeutic treatments for germ cell tumors (GCTs) and subsequent development of Philadelphia chromosome–positive chronic myeloid leukemia (CML).

GCTs are the most common malignancy among young men (ages 15 to 35), and the tumors are remarkably responsive to chemotherapy. In fact, cure rates of these tumors approach 80%. “Late adverse effects of treatment can manifest throughout the lifetime of a cured patient who will be at increased risk of solid and hematologic malignant neoplasms,” wrote authors of a research letter, led by Nabil Adra, MD, of the Indiana University School of Medicine in Indianapolis.

Etoposide has become an important drug in the treatment of GCTs, and it carries a known risk of secondary leukemia, typically acute myeloid leukemia manifesting with a short latency period and marked by specific chromosomal translocations. In the research letter, the authors report a case series of three individuals treated for GCTs who went on to develop CML, with varying periods of latency.

In the first case, in 1999 a man in his mid-30s was treated first with orchiectomy and then with four courses of bleomycin, etoposide, and cisplatin. More than a decade later, in 2011, he was found to have a low white blood cell count and was then diagnosed with chronic-phase CML. Though he achieved complete remission with imatinib, he later developed a neuroendocrine carcinoma with unresectable hepatic metastases and died of his disease.

The second case involved a man in his early 30s diagnosed in 2006 with nonseminomatous GCT. He also underwent orchiectomy, and then received 1 cycle of the same regimen of bleomycin, etoposide, and cisplatin. That same year his disease relapsed and he received 3 cycles of etoposide, ifosfamide, and cisplatin, followed by another relapse in 2007 when he received high-dose carboplatin and etoposide followed by peripheral blood stem cell rescue. He was found to have leukocytosis in 2011, and was diagnosed with chronic-phase CML. This patient achieved remission with dasatinib and remains in remission.

Finally, a patient developed CML with much less time after GCT treatment. He was diagnosed with GCT and treated in 2012 with 4 cycles of etoposide, ifosfamide, and cisplatin. He was also found to have leukocytosis and CML only 2 years later, in 2014. Dasatinib also allowed him to achieve and maintain remission from CML.

The authors wrote that a literature review revealed seven previous cases as well. “These findings raise the question of a causal relationship between etoposide and/or platinum-containing chemotherapy and the development of CML.” They added that the relatively low risk of developing CML following the potentially curative GCT treatment is reassuring. “However, physicians should be aware of possible late toxic effects of these treatment regimens and the need for diligent follow-up in these patients,” they concluded.