A 62-year-old male presented with a cutaneous tumor on the left arm and lymphadenopathy in the left axilla. Skin biopsy showed a diffuse infiltration of tumor cells with immunoblastoid cytomorphology. The cells were positive for CD4, CD123, TCL1, and MYC and partly positive for CD56 (Fig. 1A-G); but negative for CD3, CD20, CD79a, terminal deoxynucleotidyl transferase (TdT), myeloperoxidase (MPO), CD34, and the Epstein-Barr encoding region. In split fluorescence in situ hybridization (FISH) assay, tumor cells were positive for 8q24 (MYC locus) rearrangement but negative for SUPT3H and MYB rearrangements (Fig. 2). The present patient was diagnosed with BPDCN according to the diagnostic criteria proposed by Julia et al.. Peripheral blood yielded a hemoglobin level of 14.4 g/dL, a leukocyte count of 6.6 x 103/muL and a platelet count of 13.5 x 104/muL. Bone marrow examination showed 92% blast cells (Fig. 1H), of which MPO activity was not detected by the diaminobenzidine method. Flow cytometry analysis revealed that the leukemic cells were positive for CD4, CD33, CD123, interleukin-3 receptor, human leukocyte antigen (HLA)-DR, and CD45RA, partly positive for CD56 and negative for TdT and cytoplasmic MPO. G-banding analysis showed del(13)(q12q22) in 7 out of 16 metaphase cells. Rearrangements of the T cell receptor gamma-chain gene by polymerase chain reaction (PCR) analysis and immunoglobulin heavy-chain genes by Southern blotting analysis were not detected. These findings confirmed bone marrow involvement of BPDCN. The induction chemotherapy was initiated with daunorubicin 50 mg/m2 daily for 5 days and cytarabine 100 mg/m2 daily for 7 days, resulting in complete hematological remission (CR). Subsequently, he received 2 courses of consolidation chemotherapy. The patient did not have a related donor who was serologically HLA-matched. Thus, he was transplanted with unrelated bone marrow from a male donor (total nucleated cell dose, 3.4 x 108 cells/kg; genotypically matched for HLA-A, -B, -Cw, and -DR1) from the Japan Marrow Donor Program using a RIC regimen with total body irradiation (TBI) 2 Gy / 1 fraction, fludarabine (Flu) 125 mg/m2, and melphalan (Mel) 80 mg/m2. A combination of tacrolimus (Tac) and short-term methotrexate (sMTX) was used as graft-versus-host disease (GVHD) prophylaxis. Neutrophil engraftment (absolute neutrophil count of at least >0.5 x 109/L for 3 consecutive points) and platelet recovery (platelet count of >50 x 109/l without transfusion for 3 consecutive points) were obtained on days +15 and +30 after transplantation, respectively. He maintained CR without any symptoms of GVHD.
Four months after the initial transplantation, he developed two cutaneous tumors on his legs. Skin biopsy showed the infiltration of tumor cells but bone marrow aspiration showed no evidence of relapse, which confirmed extramedullary relapse of BPDCN. Despite the cessation of Tac, lymphadenopathy in the left inguinal was noted. At day 180 after allo-HSCT, bone marrow examination revealed 10% leukemic cells, and short tandem repeat DNA analysis showed 5.5% recipient-type cells at day 180, indicating a progression to hematological relapse of BPDCN. He achieved partial remission after 1 course of re-induction chemotherapy with daily cyclophosphamide 600 mg/m2 on day 1, vincristine 1.3 mg/m2 on days 1, 8, 15, 22, doxorubicin 20 mg/m2 on days 1 to 3, prednisolone 60 mg/body po on days 1 to 7 (then tapered for 28 days) and L-asparaginase 2000 IU/m2 div on days 11, 13, 18, 21. The patient was transplanted with HLA-matched unrelated male bone marrow (total nucleated cell dose, 2.3 x 108 cells/kg; genotypically matched for HLA-A, -B, -Cw and -DR1) followed by a RIC regimen with Flu 30 mg/m2 daily for 5 days, intravenous busulfan (BU) 3.2 mg/kg daily for 2 days, and TBI 2 Gy / 1 fraction. Tac and sMTX were administered as prophylaxis against GVHD. Ten days after the second transplantation (before neutrophil engraftment), he presented with stridor due to severe laryngeal irritation, and underwent mechanical ventilation. Neutrophil engraftment and platelet recovery were achieved on days +21 and +127 after the second transplantation, respectively. He achieved the second CR of BPDCN with complete second-donor chimerism. He developed grade II acute GVHD with stage 2 skin involvement 48 days after transplantation, but did not require additional immunosuppressive treatment, such as systemic administration of corticosteroid. He presented lichen planus-like features in the skin and oral mucosa due to moderate chronic GVHD. He started anti-androgen therapy for localized prostate cancer at day +1525. During anti-androgen therapy, he did not experience any symptom of relapse disease of BPDCN. Furthermore, chronic GVHD in oral mucosa and skin persisted without progression in any other organ, and a lymphocyte count was maintained between 3.01 and 4.41 x 109/L. The withdrawal of immunosuppressants was performed on day +1748. He was alive without any symptom of relapse more than 71 months after the second allo-HSCT.