Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological neoplasm predominantly afflicting older males (median age; 66–70 years), frequently characterized by a cutaneous, lymph node, bone marrow, and/or central nervous system (CNS) involvement with dismal outcomes.^{1, 2} Tagraxofusp, a CD123 directed antibody conjugate composed of human interleukin-3 (IL-3) and truncated diphtheria toxin, is an approved therapy for BPDCN, with high response rates of 90% and 67% among untreated patients and those with relapsed disease, respectively.³ Nonetheless, survival continues to be compromised with 24-month overall survival of 52% and median overall survival of 8.5 months in treatment naïve and relapsed patients, respectively.³ Moreover, treatment-induced toxicities are not uncommon with potential for fatality; hepatotoxicity (64%), hypoalbuminemia (55%), thrombocytopenia (49%), and capillary leak syndrome (19%).³ Notably, not all patients with BPDCN will be eligible for CD123-targeted therapy as in the setting of baseline severe hypoalbuminemia, cardiac co-morbidities, or renal insufficiency. Furthermore, the widespread availability of CD123-targeted agents beyond the US and EU is not common. Allogeneic stem cell transplantation (SCT) can result in long-term remissions for selected younger/fit patients with BPDCN but given the older median age and significant co-morbidities in many real-world patients with BPDCN, SCT is often not an option.⁴ Interestingly, in pre-clinical investigations, BPDCN cells depicted BCL-2 dependence,⁵ and epigenetic dysregulation^6-9 and treatment with venetoclax have been administered as monotherapy or in combination with chemotherapy in small series of patients.¹⁰ Venetoclax (Ven), an oral BCL-2 inhibitor in combination with hypomethylating agents (HMA) is approved for elderly and/or unfit acute myeloid leukemia (AML).^11-13 Accordingly, we share our experience with Ven and HMA in 10 patients (median age; 70 years [range; 22–82 years]) with BPDCN treated at the Mayo Clinic (Rochester, MN [n = 3], Arizona [n = 1], Florida [n = 1]), and MD Anderson Cancer Center (n = 5). Study patients were retrospectively recruited after respective institutional review board approval. Diagnosis was established by skin, lymph node, or bone marrow biopsy. In addition, all patients underwent positron emission tomography (PET) imaging and cerebrospinal fluid sampling to evaluate for nodal and CNS disease.

Table 1 summarizes clinical characteristics including treatment details for all 10 BPDCN patients treated with Ven + HMA. Notably, the majority of patients had baseline co-morbidities, including renal failure, cardiac disease, hypoalbuminemia, hepato-biliary disease that limited upfront CD123-targeted and clinical trial-based therapy. It is, therefore, an urgent unmet medical need to investigate non-CD123-based and noncytotoxic chemotherapy regimens that can be safely delivered in the setting of extensive co-morbidities in older/unfit patients with BPDCN.^{14, 15} All patients in this case series that were offered treatment with HMA + VEN in the front-line or for relapsed disease responded to therapy, although responses were short-lived, two patients proceeded to allogeneic SCT, and transplant is forthcoming for another patient. A detailed overview of five patients treated at the Mayo Clinic is provided below.

Patient #1: A 67-year-old gentleman presented with a raised nodular skin rash involving the right lower flank region, which extended to involve the trunk, proximal thighs, and face. Skin biopsy confirmed BPDCN with neoplastic cells weakly positive for CD123 and CD56 with expression of CD4, CD43, and TCL1. Hemoglobin was 11.5 g/dL, white cell count 4.1 × 10⁹/L, absolute neutrophil count (ANC) 2.3, 56% monocytes, and platelet count of 122 × 10⁹/L. Bone marrow biopsy was noted to be 50% cellular with left-shifted granulopoiesis and 4% blasts, without morphological evidence for BPDCN. Karyotype was normal and ASXL1 p.Gly646TrpfsX12 (36%) mutation was noted, in addition to TET2 p.Try1255X (69%), p.Met804ArgfsX9 (13%) and two ZRSR2 variants, D185G, and in-frame exon 11 deletion. He initiated therapy with azacitidine 75 mg/m² days 1–7 and Ven 400 mg for 28 days with dramatic improvement of cutaneous lesions after cycle one, achieving complete response after 2 cycles without treatment-emergent complications. He proceeded to a haplo-identical allogeneic transplant and remains disease-free 17 months after diagnosis.

Patient #2: Sixty-six-year male presented with a 6-month history of progressively enlarging nodular lesion on his back and emergence of multiple lesions on his trunk and upper extremities. Left chest wall lesion biopsy was positive for CD56, CD123, CD303, TCL1A, and CD4. Hemoglobin was 13.5 g/dL, white count 3.8 × 10⁹/L, 17% monocytes, and platelet count of 106 × 10⁹/L. Bone marrow biopsy showed slight megakaryocytic atypia, slight increase in monocytes, and 3% blasts without morphologic evidence of BPDCN. Next-generation sequencing with ASXL1: c.1934dup; p.Gly646Trpfs*12 (29%) mutation and variants of unknown significance (VUS); SH2B3:c.107C>A; p.Ala36Glu (48%) TERT: c.1552G>T; p.Ala518Ser (50%) and TET2:c.3530T>G; and p.Ile1177Ser (58%). He received azacitidine 75 mg/m² × 7 days, and Ven 400 mg daily, achieving a major cutaneous response after cycle 1. He developed prolonged cytopenias, and after cycle 5, had a treatment hiatus of 3 months due to reactivation of latent tuberculosis. During the latter phase, new skin lesions emerged after which sixth cycle of azacitidine for 7 days and Ven 100 mg × 28 days was administered with marked improvement in skin lesions. He is currently receiving cycle seven of azacitidine and Ven, awaiting a matched unrelated donor allogeneic SCT.

Patient #3: A 65-year-old gentleman presented with a 2-week history of rash, fever, and weight loss. Hemoglobin was 7.2 g/dL, white count 1.2 × 10⁹/L, ANC 0.39, and platelet count of 163 × 10⁹/L. PET scan showed hypermetabolic lymphadenopathy, involving bilateral cervical, axillary, inguinal, periportal, and retroperitoneal nodes. Right shoulder skin biopsy was positive for CD4, CD123 consistent with BPDCN, and right axillary lymph node biopsy was also confirmatory. Bone marrow biopsy with 50% blasts, cytogenetics with trisomy 13, molecular studies revealed RUNX1: c.416G>A; p.Arg139Gln(15%), SF3B1: c.1998G>C; p.Lys666Asn(38%); and SRSF2: c.284C>G;p.Pro95Arg (34%) mutations. Due to transaminitis, he was initiated on azacitidine 75 mg/m² × 7 days and Ven 100 mg daily × 28 days. Following cycle 1, complete marrow response with cytogenetic and molecular remission, near-complete resolution of adenopathy, and major skin response was achieved. However, new skin lesions emerged on day 12, cycle 2 of azacitidine and Ven, biopsy-proven to be relapsed disease. Hence, tagraxofusp was instituted, at 12 μg/kg daily × 3 doses, following which he developed fatal capillary leak syndrome.

Patient #4: A 78-year-old gentleman presented with a 6-month history of a progressive skin rash; biopsy was positive for CD 45, BCL2, CD56, CD123, TCL1A, and CD33 consistent with BPDCN.

White cell count was 4.4 × 10⁹/L with 16% circulating blasts, platelets of 40 × 10⁹/L, and hemoglobin of 12.2 g/dL. Bone marrow biopsy with 84% blasts consistent with BPDCN, with complex monosomal karyotype, and ASXL1: c.2324T>A; p.Leu775 (18%), SRSF2: c.284C>G; p.Pro95Arg (29%), TET2: c.4393C>T; p.Arg1465 (29%) mutations. PET/CT scan revealed involvement of lymph nodes in the neck, axillae, gastrohepatic, periportal regions, iliac chain, groin, and spleen. He initiated therapy with tagraxofusp, which was well-tolerated. Repeat PET imaging and bone marrow biopsy following cycle 2 of tagraxofusp demonstrated complete response with cytogenetic remission. In addition, skin lesions resolved but re-emerged after cycle 5 of tagraxofusp. He received cycle 1 of decitabine 20 mg/m² × 5 days and Ven 400 mg × 28 days and attained a major skin response. During cycle 4, Ven was discontinued after 14 days due to cytopenias. Soon thereafter new skin lesions emerged after 3 months of achieving complete remission (CR). He received salvage therapy with one cycle of cladribine but unfortunately succumbed to progressive disease.

Patient #5: A 22-year-old female presented with severe back pain. MRI spine without intramedullary or leptomeningeal enhancement but bone marrow was diffusely T1 hypodense. Blood counts on presentation were as follows; white count 27 × 10⁹/L with 70% blasts, hemoglobin 9.5 g/dL, and platelet count 85 × 10⁹/L. Peripheral blood flow cytometry revealed a distinct population expressing CD4, CD123, partial CD7 (dim), CD22, CD38 (low density), CD56, and HLA-DR. Bone marrow biopsy was consistent with BPDCN. PET imaging with bilateral axillary, mediastinal, retroperitoneal adenopathy, and mild splenomegaly. Initial therapy comprised of hyper fractioned cyclophosphamide, vincristine, adriamycin, dexamethasone (hyper-CVAD), which led to resolution of adenopathy, but persistent marrow disease. She received salvage cladribine, cytosine arabinoside, G-CSF, mitoxantrone, which led to CR, followed by consolidation with etoposide, cytosine arabinoside. Unfortunately, bone marrow biopsy after consolidation showed relapse for which she received decitabine 20 mg/m² × 5 days and Ven 400 mg × 28 days for a total of 6 cycles, achieving remission after cycle 5, and proceeded with matched unrelated allogeneic transplant in CR2. Unfortunately, she relapsed 9 months post-transplant, was treated with tagraxofusp × 4 cycles, as a bridge to second matched related donor allogeneic transplant. She relapsed a year following second transplant, began salvage therapy with hyper-CVAD and Ven but died during cycle one as a result of sepsis and progressive disease.

The literature on Ven plus HMA therapy for BPDCN is limited to a few patients treated with either Ven as a single agent, HMA alone, or as combination therapy. Ven monotherapy in two older patients with relapsed/refractory BPDCN, and cutaneous, nodal, and marrow involvement and prior therapies, including modified hyper-CVAD, IL-3 directed therapy, led to remarkable cutaneous response, partial nodal response but without marrow response at week 4 in patient one.⁵ Unfortunately, treatment was complicated by intracranial hemorrhage as a result of thrombocytopenia, which led to his demise.⁵ Similarly, a second patient also demonstrated a dramatic skin and nodal response, with partial marrow response at week 4, and continued on therapy for 12 weeks until disease progression.⁵ Notably, in a subsequent report of a 62-year female with cutaneous, nodal, and marrow involvement, previously received bortezomib and simvastatin, Ven treatment resulted in marrow response in 1 month, and complete nodal response at 6 months, which was ongoing at 9 months.¹⁶

With regard to azacitidine monotherapy, two elderly patients with BPDCN and concomitant myelodysplastic syndrome, achieved rapid improvement of skin lesions and stabilization of counts, but infectious complications resulted from neutropenia, after the fourth and fifth cycle of therapy, eventually leading to demise in both cases.¹⁷ In another series of three BPDCN patients that received azacitidine, similar short-lived responses were reported, with median overall survival of 17 months.¹⁸ Similarly, Ven + HMA or cytarabine in two heavily pretreated BPDCN patients, resulted in major nodal response, partial marrow response, and improvement in skin lesions in one patient; and the second patient achieved a major skin response.¹⁹ Two additional cases have since been reported, the first case with skin, lymph node, and marrow involvement and documented CR after hyper-CVAD (3 cycles), experienced cutaneous relapse, but achieved a rapid response by cycle 1 day 14 of Ven + azacitidine, which was durable at 8 months.²⁰ Another patient with cutaneous relapse following tagraxofusp, achieved major skin response following 2 cycles of Ven and azacitidine, which is ongoing at cycle 5.²¹

In conclusion, the current series, which is one of the largest compilations of BPDCN patients treated with Ven + HMA off-protocol, confirms clinical efficacy and safety of the regimen, which may serve as a bridge to allogeneic transplant. As in older patients with AML that are unfit for cytotoxic chemotherapy, the HMA + VEN combination may be a feasible alternative to CD123-directed or cytotoxic chemotherapy in patients with BPDCN and extensive co-morbidities. For fit patients, results from ongoing clinical trials featuring combination therapies in doublets and triplets, evaluating Ven with decitabine, and Ven and azacitidine together with tagraxofusp in the relapsed setting are awaited.^22-26

母细胞性浆细胞样树突状细胞肿瘤 (BPDCN) 是一种侵袭性血液肿瘤，主要累及老年男性（中位年龄；66-70 岁），通常以皮肤、淋巴结、骨髓和/或中枢神经系统 (CNS) 受累为特征结果惨淡。^{1, 2} Tagraxofusp 是一种由人白介素 3 (IL-3) 和截短的白喉毒素组成的 CD123 定向抗体偶联物，是一种获批的 BPDCN 疗法，在未治疗患者和复发患者中的反应率分别高达 90% 和 67%疾病，分别。³尽管如此，未接受治疗和复发患者的 24 个月总生存期和中位总生存期分别为 52% 和 8.5 个月，生存率继续受到影响。³此外，治疗引起的毒性并不少见，并有可能导致死亡。肝毒性（64%）、低白蛋白血症（55%）、血小板减少症（49%）和毛细血管渗漏综合征（19%）。³值得注意的是，并非所有 BPDCN 患者都符合 CD123 靶向治疗的条件，如在基线严重低白蛋白血症、心脏合并症或肾功能不全的情况下。此外，CD123 靶向药物在美国和欧盟以外的广泛使用并不常见。同种异体干细胞移植 (SCT) 可以使选定的年轻/健康的 BPDCN 患者获得长期缓解，但考虑到许多现实世界 BPDCN 患者的中位年龄较大和明显的合并症，SCT 通常不是一种选择。⁴有趣的是，在临床前研究中，BPDCN 细胞描述了 BCL-2 依赖性⁵和表观遗传失调^6-9和 venetoclax 治疗已作为单一疗法或与小范围患者的化学疗法联合使用。¹⁰ Venetoclax (Ven) 是一种与低甲基化剂 (HMA) 联用的口服 BCL-2 抑制剂，已被批准用于老年人和/或不适的急性髓性白血病 (AML)。^11-13因此，我们分享了在梅奥诊所（明尼苏达州罗切斯特 [ n  = 3]，亚利桑那州 [ n  = 1]、佛罗里达州 [ n  = 1]）和 MD 安德森癌症中心（n  = 5)。在各自的机构审查委员会批准后，回顾性招募了研究患者。通过皮肤、淋巴结或骨髓活检确定诊断。此外，所有患者均接受了正电子发射断层扫描 (PET) 成像和脑脊液采样，以评估淋巴结和 CNS 疾病。

表 1 总结了所有 10 名接受 Ven + HMA 治疗的 BPDCN 患者的临床特征，包括治疗细节。值得注意的是，大多数患者有基线合并症，包括肾功能衰竭、心脏病、低白蛋白血症、肝胆疾病，这些疾病限制了前期 CD123 靶向治疗和基于临床试验的治疗。因此，迫切需要研究非 CD123 和非细胞毒性化疗方案，这些方案可以在老年/不健康 BPDCN 患者广泛合并症的情况下安全实施。^14、15该病例系列中所有在一线接受 HMA + VEN 治疗或复发疾病的患者都对治疗产生了反应，尽管反应是短暂的，两名患者进行了同种异体 SCT，另一名患者即将进行移植。下面提供了在梅奥诊所接受治疗的五名患者的详细概述。

患者 #1：一位 67 岁的男性出现了累及右下腹区域的隆起结节性皮疹，并延伸至躯干、大腿近端和面部。皮肤活检证实 BPDCN，肿瘤细胞 CD123 和 CD56 呈弱阳性，CD4、CD43 和 TCL1 表达。血红蛋白为 11.5 g/dL，白细胞计数为 4.1 × 10 ⁹ /L，中性粒细胞绝对计数 (ANC) 为 2.3，单核细胞为 56%，血小板计数为 122 × 10 ⁹ /L。骨髓活检有 50% 的细胞，有左移的粒细胞生成和 4% 的原始细胞，没有 BPDCN 的形态学证据。除了TET2 p.Try1255X (69%)、p.Met804ArgfsX9 (13%) 和两个ZRSR2变体、D185G 和框内外显子 11 缺失。他开始使用阿扎胞苷 75 mg/m ^{2 第}1-7 天和 Ven 400 mg 治疗 28 天，在第一个周期后皮肤病变显着改善，在 2 个周期后达到完全缓解，没有治疗出现的并发症。他进行了单倍体同种异体移植，并在诊断后 17 个月保持无病状态。

患者 #2：66 岁男性，有 6 个月的背部逐渐扩大的结节性病变以及躯干和上肢出现多处病变的病史。左胸壁病变活检 CD56、CD123、CD303、TCL1A 和 CD4 阳性。血红蛋白13.5 g/dL，白细胞计数3.8 × 10 ⁹ /L，单核细胞17%，血小板计数106 × 10 ⁹ /L。骨髓活检显示有轻微的巨核细胞异型性，单核细胞略有增加，3% 的原始细胞没有 BPDCN 的形态学证据。使用ASXL1进行下一代测序：c.1934dup；p.Gly646Trpfs*12 (29%) 突变和意义不明的变体 (VUS)；SH2B3 :c.107C>A; p.Ala36Glu (48%)叔: c.1552G>T; p.Ala518Ser (50%) 和TET2 :c.3530T>G; 和 p.Ile1177Ser (58%)。他接受了阿扎胞苷 75 mg/m ²  × 7 天和每天 400 mg 的静脉注射，在第 1 个周期后实现了主要的皮肤反应。他出现长时间的血细胞减少，在第 5 个周期后，由于潜伏性结核病的重新激活，治疗中断了 3 个月. 在后期，出现新的皮损，之后第 6 周期阿扎胞苷 7 天和 Ven 100 mg × 28 天给药，皮损明显改善。他目前正在接受阿扎胞苷和 Ven 的第七周期，等待匹配的无关供体同种异体 SCT。

患者 #3：一位 65 岁的男士，因皮疹、发烧和体重减轻 2 周而就诊。血红蛋白为 7.2 g/dL，白细胞计数为 1.2 × 10 ⁹ /L，ANC 为 0.39，血小板计数为 163 × 10 ⁹ /L。PET 扫描显示高代谢淋巴结肿大，累及双侧颈部、腋窝、腹股沟、门静脉周围和腹膜后淋巴结。右肩皮肤活检CD4、CD123阳性与BPDCN一致，右腋窝淋巴结活检也确诊。50% 原始细胞的骨髓活检，13 三体细胞遗传学，分子研究显示RUNX1：c.416G>A；p.Arg139Gln(15%)，SF3B1：c.1998G>C；p.Lys666Asn(38%)；和SRSF2: c.284C>G;p.Pro95Arg (34%) 突变。由于转氨炎，他开始使用阿扎胞苷 75 mg/m ²  × 7 天和 Ven 100 mg 每天 × 28 天。在第 1 个周期后，实现了具有细胞遗传学和分子缓解的完全骨髓反应、几乎完全消退的腺病和主要的皮肤反应。然而，在阿扎胞苷和 Ven 的第 2 周期第 12 天出现了新的皮损，活检证实为复发性疾病。因此，开始服用tagraxofusp，每天12μg/kg×3次，随后他出现了致命的毛细血管渗漏综合征。

患者 #4：一位 78 岁的绅士，出现 6 个月的进行性皮疹病史；CD 45、BCL2、CD56、CD123、TCL1A 和 CD33 活检呈阳性，与 BPDCN 一致。

白细胞计数为 4.4 × 10 ⁹ /L，循环原始细胞为 16%，血小板为 40 × 10 ⁹ /L，血红蛋白为 12.2 g/dL。骨髓活检 84% 原始细胞与 BPDCN 一致，具有复杂的单体核型，并且ASXL1：c.2324T>A；p.Leu775 (18%)，SRSF2：c.284C>G；p.Pro95Arg (29%), TET2: c.4393C>T; p.Arg1465 (29%) 突变。PET/CT 扫描显示颈部、腋窝、胃肝、门静脉周围区域、髂链、腹股沟和脾脏的淋巴结受累。他开始使用耐受性良好的tagraxofusp进行治疗。在tagraxofusp 2周期后重复PET成像和骨髓活检显示细胞遗传学缓解的完全反应。此外，皮肤损伤在tagraxofusp 5 周期后消退但又重新出现。他接受了第 1 周期 20 mg/m ^{2的地西他滨} × 5 天和 Ven 400 mg × 28 天并获得主要的皮肤反应。在第 4 周期期间，Ven 在 14 天后因血细胞减少而停药。此后不久，在达到完全缓解 (CR) 的 3 个月后出现了新的皮肤损伤。他接受了一周期克拉屈滨的抢救治疗，但不幸死于进展性疾病。

患者 #5：一名 22 岁的女性出现严重的背痛。MRI脊柱无髓内或软脑膜强化，但骨髓呈弥漫性T1低密度。就诊时的血细胞计数如下；白细胞计数 27 × 10 ⁹ /L，原始细胞 70%，血红蛋白 9.5 g/dL，血小板计数 85 × 10 ⁹/L。外周血流式细胞术显示表达 CD4、CD123、部分 CD7（暗淡）、CD22、CD38（低密度）、CD56 和 HLA-DR 的不同群体。骨髓活检与 BPDCN 一致。双侧腋窝、纵隔、腹膜后淋巴结肿大和轻度脾肿大的 PET 成像。初始治疗包括超分割环磷酰胺、长春新碱、阿霉素、地塞米松（hyper-CVAD），导致淋巴结肿大消退，但骨髓疾病持续存在。她接受了挽救性克拉屈滨、阿糖胞苷、G-CSF、米托蒽醌，这导致了 CR，然后用依托泊苷、阿糖胞苷巩固。不幸的是，巩固后的骨髓活检显示复发，她接受了 20 mg/m ^{2的地西他滨治疗} × 5 天和 Ven 400 mg × 28 天共 6 个周期，第 5 个周期后达到缓解，并在 CR2 中进行匹配的无关异基因移植。不幸的是，她在移植后 9 个月复发，接受了 tagraxofusp × 4 个周期的治疗，作为第二次匹配的相关供体同种异体移植的桥梁。她在第二次移植后一年复发，开始使用 hyper-CVAD 和 Ven 进行抢救治疗，但在第一周期因败血症和进行性疾病而死亡。

关于 Ven 加 HMA 治疗 BPDCN 的文献仅限于少数使用 Ven 作为单一药物、单独使用 HMA 或作为联合治疗的患者。两名患有复发/难治性 BPDCN、皮肤、淋巴结和骨髓受累的老年患者的静脉单药治疗和先前的治疗，包括改良的超 CVAD、IL-3 定向治疗，导致显着的皮肤反应、部分淋巴结反应，但在第 4 周患者一号。⁵不幸的是，由于血小板减少症导致颅内出血，治疗变得复杂，导致他死亡。⁵同样，第二名患者也表现出显着的皮肤和淋巴结反应，在第 4 周出现部分骨髓反应，并继续治疗 12 周直至疾病进展。⁵值得注意的是，在随后的报告中，一名 62 岁女性患有皮肤、淋巴结和骨髓受累，之前接受过硼替佐米和辛伐他汀治疗，Ven 治疗在 1 个月内导致骨髓反应，在 6 个月时完全淋巴结反应，这在 9个月。¹⁶

阿扎胞苷单药治疗，两名老年BPDCN合并骨髓增生异常综合征患者，皮损迅速改善，计数稳定，但中性粒细胞减少引起感染性并发症，经过第四、五周期治疗，最终均死亡. ¹⁷在另一系列的三名接受阿扎胞苷的 BPDCN 患者中，报告了类似的短期反应，中位总生存期为 17 个月。¹⁸同样，在两名经过大量预处理的 BPDCN 患者中，Ven + HMA 或阿糖胞苷导致一名患者的主要淋巴结反应、部分骨髓反应和皮肤病变改善；第二名患者获得了主要的皮肤反应。¹⁹此后报告了另外两例病例，第一例皮肤、淋巴结和骨髓受累，并在 hyper-CVAD（3 个周期）后记录 CR，经历了皮肤复发，但在 Ven + 阿扎胞苷的第 1 天第 14 周期实现了快速反应，可使用 8 个月。²⁰另一名在tagraxofusp 后出现皮肤复发的患者，在使用 Ven 和阿扎胞苷的 2 个周期后获得了主要的皮肤反应，该周期在第 5 个周期进行^。21

总之，目前的系列是接受 Ven + HMA 非方案治疗的 BPDCN 患者的最大汇编之一，证实了该方案的临床疗效和安全性，可作为同种异体移植的桥梁。与不适合细胞毒性化疗的老年 AML 患者一样，HMA + VEN 组合可能是 BPDCN 和广泛合并症患者 CD123 定向或细胞毒性化疗的可行替代方案。对于健康的患者，正在等待正在进行的临床试验的结果，该试验的特点是双联疗法和三联疗法，在复发情况下评估 Ven 与地西他滨，以及 Ven 和阿扎胞苷与他格司普。^22-26