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.