Case
The 75-year-old male patient was diagnosed with CML 25 years ago (in August 1994) and he started a treatment with interferon. Twelve years later, the patient was started on imatinib. In October 2009, he gradually developed cytopenia. Although there were approximately 3% blasts in the bone marrow, cytogenetic analysis revealed double Ph clones, Therefore, the patient was diagnosed with an accelerated phase of CML and the treatment was switched to nilotinib. A cytogenetic response was achieved 3 months after starting treatment with nilotinib, and a major molecular response (MMR) was achieved 2 years after starting nilotinib dosing. The patient developed erythema on the extremities and trunk from the start of nilotinib dosing and antihistamines were continuously administered; however, because the eruptions became uncontrollable, the treatment was changed to bosutinib in March 2016. The MMR was maintained even after switching to bosutinib.
In early August 2019, the patient developed a posterior neck pain and malaise and was seen at a local medical institution. Computed tomography (CT) revealed lymphadenopathies in the bilateral cervical, mediastinal, and gastric cardial regions, and also around the pancreas head and bilateral inguinal regions. Positron emission tomography showed abnormal accumulation of fluorodeoxyglucose at these same sites (Figure 1). Pathological examinations of the inguinal lymph node biopsies showed cells with large nuclei, proliferating in a starry sky pattern, and immunostaining revealed CD19(+), CD20(+), CD79a(+), MUM1(+), BCL-2(+), c-myc(+), strongly positive Ki-67, CD10(−), TdT(−), and EBER(−). There was no bone marrow infiltration and the patient was diagnosed with a stage III HGBCL. Administration of bosutinib was discontinued since BCR-ABL1 transcript copies remained below the level of detection achieved by the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). After two courses of the dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) therapy, a complete remission (CR) was confirmed on CT scan. The CR was also maintained after 4 additional courses (a total of 6 courses) of the same therapy. Moreover, BCR-ABL1 transcript copies remained undetectable by RT-PCR 8 months after bosutinib discontinuation.