Therapy-related acute myeloid leukemia and myelodysplastic syndrome among refractory germ cell tumor patients

Int J Urol. 2018 Jul;25(7):678-683. doi: 10.1111/iju.13597. Epub 2018 May 11.

Abstract

Objectives: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience.

Methods: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed.

Results: Four testicular tumor patients (4/171, 2.3%) developed therapy-related acute myeloid leukemia and myelodysplastic syndrome. Three of them were affected after complete remission of the primary testicular tumor. A median time interval from a start of chemotherapy to a secondary tumor development was 6.8 years (range 3.7-11.5 years). The median total dose of etoposide, ifosfamide, cisplatin and nedaplatin were 3640 mg/m2 (range 2906-4000 mg/m2 ), 42.7 g (range 19.5-54.0 g), 1100 mg/m2 (range 600-1500 mg/m2 ) and 500 mg/m2 (range 300-1600 mg/m2 ), respectively. Etoposide had the only significant relationship between a cumulative dose and leukemogenesis in univariate analysis (P < 0.05). One patient had complete remission, but the other three patients died.

Conclusions: The present findings show that refractory germ cell tumor patients have an increased risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome. A cumulative dose of etoposide is a significant risk of leukemogenesis. As therapy-related acute myeloid leukemia and myelodysplastic syndrome has a poor prognosis, close follow up is required for refractory germ cell tumor patients.

Keywords: extragonadal tumor; leukemogenesis; refractory germ cell tumor; testicular tumor; therapy-related acute myeloid leukemia and myelodysplastic syndrome.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Follow-Up Studies
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / epidemiology*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / chemically induced
  • Myelodysplastic Syndromes / epidemiology*
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / epidemiology*
  • Retrospective Studies
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Etoposide
  • Cisplatin
  • Ifosfamide