A 56-year-old man was admitted to our hospital at the beginning of June 2020 because of repeated fever for one month. The patient complained of repeated fever in the past month, with the temperature mostly around 38°C, and the temperature usually dropped in the middle of the night. What’s more, fever was accompanied by no symptoms other than a mild headache.
Blood routine examination revealed pancytopenia in the patient (white blood cell counts 3.31*109/L, 54.7% neutrophil, 26.9% lymphocytes, 17.8% monocytes; hemoglobin 84g/L; platelets 67*109/L). Coagulation studies showed the international standardized ratio (INR) (1.21) and fibrinogen (6.15) increased, the others including thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) were normal. Ferritin rose to 2,931.94 ng/ml. Lactate dehydrogenase (LDH) was slightly up to 582 U/L. In addition, we screened some infectious diseases and identified common bacteria, fungi, viruses and special pathogens such as Mycobacterium tuberculosis in blood, urine, feces, cerebrospinal fluid and alveolar lavage fluid specimens.
All the evidence pointed to blood system disorder, so we performed a bone marrow puncture and refined the positron emission tomography / computed tomography (PET/CT). Pathological hematopoiesis was found in the patient's first bone marrow smear (Fig. 1a), and the flow cytometry (FCM) revealed that abnormal myeloid cells accounted for 5.84%, with CD117, CD34, CD33, CD13 and HLADR positive (Fig. 2a), indicating myelodysplastic syndrome (MDS). Immunohistochemistry showed MPO(-), CD138(-), CD235(+), CD117(-), CD34(+), CD19(-), CD61(+). PET/CT found that 18F-flurodeoxyglucose (18F-FDG) metabolism in the scanning area of the medullary cavity was diffusely increased; liver was not large, 18F-FDG metabolism was slightly increased; spleen was enlarged, 18F-FDG metabolism was increased, suggesting hematological disease. We changed the site and then performed bone marrow puncture again. Bone marrow smear showed 6% of primitive lymphoid cells and 1% of phagocytic reticular cells (Fig. 1b). FCM found abnormal myeloid cells accounted for 6.71%, with CD117, CD34, CD33, CD13, HLADR and CD38 positive (Fig. 2b). Bone marrow biopsy revealed slightly lower hematopoietic hyperplasia, and immunohistochemical staining results were the same as the first time. On June 23th, we performed a third bone marrow puncture. This report suggested that the proportion of primitive megakaryocytes increased to 20.5%, which means the diagnosis of AMKL was made (Fig. 1c, 1d). FCM indicated abnormal myeloid cells accounted for 11.53%, with CD117, CD34, CD33, CD13, HLADR, CD123, CD61, CD41, CD42b and CD36 positive (Fig. 3). Chromosomal analysis with G-banded karyotype of bone marrow cells showed 45, XY, del(5)(q21q34),-7/46,del(3)(q25),+mar/46,sdl,del(2)(p21)/46,XY (Fig. 4). Fluorescence in situ hybridization (FISH) and real time polymerase chain reaction (RT-PCR) confirmed that BCR/ABL was positive.
Based on the above information, the patient was currently diagnosed with AMKL (MDS transformation) and hemophagocytic lymphohistiocytosis. After the internal discussion in the department and the consent of the patients, we selected decitabine combined with Bcl-2 inhibitor for the induction chemotherapy of the patients. The specific plan was as follows: decitabine 38 mg d1-5; venetoclax 100 mg d1, 200 mg d2, 400 mg d3-28. Considering that the patient was positive for BCR/ABL fusion gene, oral imatinib was added at 400 mg/day for targeted therapy. During the treatment, antiemetic, gastric protection, blood component transfusion and other symptomatic support treatment were provided. After that, the patient's body temperature gradually stabilized, and the complete blood count (CBC) increased. After the general condition improved, the patient was discharged.
At the end of the first course of treatment, the patient achieved clinical and bone marrow remission, but had a hemoglobin of 56g/ L.
Comprehensive assessment was partial remission (PR). Thankfully, the patient achieved complete remission (CR) after the second course of chemotherapy with the same regimen and without any serious adverse events (CR was defined as < 5% blast cells in bone marrow, normal hematopoiesis, the absence of blasts cells in the peripheral blood and disappearance of extramedullary infiltration) (Fig. 5). What’s more, RT-PCR showed that the M-BCR/ABL positive rate was 35% at the time of diagnosis, decreased to 13% after the second chemotherapy, and decreased to 0.024% after the third chemotherapy. After the third chemotherapy with the same regimen, the patient remained CR. However, after the fourth round of chemotherapy, the patient developed severe myelosuppression (white blood cell counts 0.65*109/L, neutrophil 0.22*109/L; hemoglobin 89g/L; platelets 24*109/L). Then came a lung infection. After symptomatic treatment, the CBC increased and the lung infection gradually improved (white blood cell counts 5.7*109/L, neutrophil 4.42*109/L; hemoglobin 90g/L; platelets 97*109/L).
To date, the patient has received a total of four cycles of chemotherapy and more than 10 months had elapsed between diagnosis and the last follow-up. We recommend that patients undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after first achieving CR. However, the patient rejected the offer because of the lack of donors, long waiting times and the huge cost.