Combination of chemotherapy and allogeneic hematopoietic stem cell transplantation for elderly patients with blastic plasmacytoid dendritic cell tumor: a case report and literature review

Combination of chemotherapy and allogeneic hematopoietic stem cell transplantation for elderly patients with blastic plasmacytoid dendritic cell tumor: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Combination of chemotherapy and allogeneic hematopoietic stem cell transplantation for elderly patients with blastic plasmacytoid dendritic cell tumor: a case report and literature review Cao Yuezhen, Gao Na, Gu Wenrong, Chu Wenhui, Li Shuo, Wang Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6975704/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly malignant hematological disease that is extremely rare in clinical practice, prone to recurrence, and has a very poor prognosis. Patients with this disease present with diverse clinical manifestations, including anemia, fever, bleeding, lymph node enlargement, and bone marrow invasion, which can easily lead to misdiagnosis as other hematological diseases. Other symptoms include skin lesions, cytopenia, bone marrow and lymph node or organ involvement. This disease often presents with skin manifestations as the first symptom, and the skin lesions are diverse, making it prone to missed diagnosis and misdiagnosis. The diagnosis of this disease usually requires a combination of clinical manifestations, imaging, histological features, and immunophenotype. Currently, there is no consensus on the first-line treatment for BPDCN. Our hospital admitted a 66-year-old male patient with the first manifestation of purple-red skin plaques and masses on the left lower extremity. The immunophenotype and histopathological characteristics were consistent with blastic plasmacytoid dendritic cell neoplasm. This report presents the therapeutic effect of chemotherapy bridging allogeneic hematopoietic stem cell transplantation in this patient and reviews relevant literature, hoping to enhance clinicians' understanding and awareness of this disease. Blastic plasmacytoid dendritic cell neoplasm BPDCN Hematological malignancy Old age Chemotherapy Allogeneic hematopoietic stem cell transplantation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Blastic plasmacytoid dendritic cell tumor, which originates from plasmacytoid dendritic cell precursor cells, is a very rare and aggressive hematological malignant disease. According to the WHO classification in 2016, BPDCN was classified as a malignant tumor of the lymphohematopoietic system [1-3] . BPDCN can involve multiple organs such as skin, central nervous system and bone marrow. In addition, it can also involve peripheral blood, lymph nodes, liver and spleen [3-5] . BPDCN is mostly treated in the department of hematology, but 90% of patients have skin lesions as the first manifestation [6] . Most of the first diagnosis departments are in the Department of dermatology, but due to its diversity of clinical manifestations, it is easy to be misdiagnosed and missed diagnosed. Therefore, the understanding level of the first diagnosis doctors in the department of dermatology is very important for the early detection, early diagnosis and early treatment of patients, so as to improve their survival cycle. As far as BPDCN tumor cells are concerned, they are often accompanied by epigenetic and cytogenetic abnormalities. However, there is no unified and effective treatment regimen. In view of the high malignant degree and poor prognosis of this disease, our department cooperated with Peking University People's Hospital to treat an elderly patient with BPDCN. The patient was treated with chemotherapy followed by allogeneic hematopoietic stem cell transplantation. allo-HSCT). In this article, we will show and summarize the clinical features, genetic characteristics, diagnosis, treatment and prognosis of the patient, and also discuss the relevant literature of the disease in recent years. 1 Clinical data The patient was a 66-year-old man. The patient presented to our department on January 12, 2019 with a complaint of "skin plaque on the left calf for more than 6 months and a left groin mass for more than 10 days". The skin plaque on the left calf (Fig 1), which was purple and accompanied by local swelling, thickening and roughness of the skin, and mild tenderness, appeared about 6 months ago without obvious causes. She presented with local swelling of the left groin and went to the outpatient department of Dermatology of our hospital for complete examination. The results of blood routine showed that: White blood cell (WBC) 3.4×10 9 /L, red blood cell (RBC) 3.7×10 12 /L, hemoglobin(Hb) 129g/L, platelet (PLT) 197×10 9 /L, lymphocyte 48.4%, neutrophil 24.8%; Local skin pathology(Fig 2): (lower leg) skin tissue examination showed that most of the epidermis was unchanged, with increased pigment in the basal layer, a large amount of mucoid material deposited in the dermal papilla and reticular layer, increased collagen in the deep layer, and chronic inflammatory cell infiltration. Mucinosis was considered, and lichen myxedematous could not be excluded. Inguinal color Doppler ultrasound showed multiple enlarged lymph nodes in the left inguinal region, the larger one was about 3.7cm×1.8cm×3.3cm, with clear boundaries, clear cortex and medulla, and thickened cortex. Ultrasound-guided needle biopsy of the left inguinal lymph nodes was performed, and the pathological results were back (Fig 3):For lymphoproliferative lesions, immuno- histochemical staining or consultation is recommended for further diagnosis, and the patient comes to our department for further diagnosis and treatment. Since the onset of the disease, the patient's consciousness was clear, the spirit was good, the diet was good, the sleep was good, there was no obvious abnormality in urine and stool, and there was no significant change in weight recently. The patient had no history of hypertension, coronary heart disease, or diabetes. He had a history of tuberculosis infection and close contact, and his father died of tuberculosis. There was no history of drug allergy. Physical examination: T: 36.7℃, P: 79 times/min, R: 18 times/min, BP: 132/97 mmHg, conscious and active, local plaque was seen on the skin of the left calf, which was purple red, accompanied by local swelling and thickening and roughness of the skin. The diameter of the mass ranged from several millimeters to several centimeters. The mass was partially isolated and partially fused, slightly elevated on the skin. The left inguinal lymph node was palpable, about 4×2×3cm in size, leathery, well demarcated from the surrounding tissue, and mobile. The breath sounds were clear in both lungs, and no dry or wet rales were heard. The abdomen was soft, and the liver and spleen were not palpable subcostal. The results of routine blood test after admission showed white blood cell count 3.5×10 9 /L, red blood cell count 3.6×10 12 /L, hemoglobin 120g/L, platelet count 193×10 9 /L, and lymphocyte percentage 36.8%. Biochemical tests showed rheumatoid factor 61.79IU/ml, IgG 1690mg/dL, and IgA 519.1mg/dL. There were no obvious abnormalities in coagulation function and five tests of hepatitis B. Echocardiography showed that the left atrium was slightly enlarged and the LVEF was 67%. Plain CT scan of the chest and upper abdomen: 1. Double pneumonia, fibrous lesions, local thickening of bilateral pleura; 2. Right pulmonary nodule; 3. Aortic and coronary artery sclerosis; 4, gastric cardia gastric wall slightly thickened; 5. Enlarged retroperitoneal lymph nodes. Bone marrow cells showed active proliferation, granulocyte + oil +, G/E=2.21:1, granulocyte ratio was normal, the proportion of promyelocytes was 2.5%, and the morphology was normal. The proportion of erythrocytes was normal, mainly middle and late juvenile red, and the morphology was normal. The proportion of lymphocytes was decreased, and immature lymphoid cells could be seen without obvious abnormal morphology. The proportion of monocytes increased. Flow cytometry showed that no primitive/immature myeloid cells with abnormal immunophenotype were detected, and no obvious expression disorder of granulocytic differentiation was observed. The pathological results of bone marrow (posterior iliac) biopsy showed active hyperplasia of bone marrow with slightly increased T and B lymphocytes (Fig 4). The PET-CT findings are shown in Figure 5（Fig 5）. The patient was diagnosed with BPDCN and received infusion port placement on 2024-1-17 and hyper-CVAD A chemotherapy on 2024-01-20 as follows: Cyclophosphamide 0.4g q12h d1-3, vincristine 2mg d4, 11, pirarubicin 60mg d4, dexamethasone 40mg d1-4, d11-14. On February 23, 2020, hyper-CVAD B regimen was given as follows: Methotrexate 2g d1, cytarabine 2g q12 d2-3, supplemented with calcium folinate rescue, hydration, alkalinization, antiemetic, acid suppression and stomach protection symptomatic and supportive treatment. During the period, delayed methotrexate metabolism and severe bone marrow suppression were observed, which gradually improved after comprehensive treatment. After two courses of chemotherapy, most of the mass in the left lower extremity flattened and decreased (Fig 6). The patient failed to receive sequential chemotherapy because of delayed methotrexate metabolism and severe bone marrow suppression after Hyper-CVAD chemotherapy. The patient was re-admitted to the hospital on 2024-04-15 for evaluation of bone marrow cells, and the morphology of bone marrow cells suggested that: The ratio of G/E was 4.23:1, and the ratio of promyelocytes and myeloblasts was 3%. The proportion of granulocytes and erythrocytes was normal, and the morphology was normal. The proportion of lymphocytes decreased and the morphology was normal. The proportion of monocytes in peripheral blood increased significantly (44%). In conclusion, considering the tendency of recurrence, the patient was changed to Azacitidine (AZA) +GemOx (AZA 100mg/d d1-7, gemcitabine 1.2g (1g/m2) d2+ oxaliplatin 120mg (100mg/m2) d2) regimen on 2024-04-16. After a course of chemotherapy with azacitidine +GemOx regimen, the patient's condition was significantly improved. The multiple skin masses originally existing in the left calf completely disappeared, and most of the skin lesions also subsided, leaving only a small amount of pigmentation, and the treatment effect was remarkable (Fig 7). On physical examination, the left inguinal lymph nodes were significantly smaller than before. The patient was reexamined by color Doppler ultrasound of superficial lymph nodes on 2024-06-11: Bilateral axillary lymph nodes were enlarged (1.5×0.7×1.2cm on the left side and 1.6×0.6×1.6cm on the right side), and bilateral cervical lymph nodes were enlarged (1.5×0.4×0.8cm on the left side and 1.4×0.4×1.1cm on the right side). Bilateral inguinal lymph nodes were enlarged (3.6×1.2×2.5cm in the left and 3.3×0.9×2.0cm in the right; The results of routine blood test showed WBC 2.7×10^9/L, RBC 2.8×10^12/L, Hb 98g/L, PLT 128×10^9/L, N% 15%. In summary, considering the recurrence of the primary disease, the patient was given azacitidine combined with GemOx regimen again on 2024-06-11. Due to the extremely malignant degree and poor prognosis of BPDCN, the patient underwent haploidentical allo-HSCT from the son to the father in Peking University People's Hospital after comprehensive consideration of the patient's condition. The stem cells were derived from the peripheral blood stem cells of the donor (the patient's son). The conditioning regimen was BU/CY+FLU+ATG+ CD25. On September 10, 2020, 321ml of donor peripheral blood was transfused, MNC: 3.082X108/kg (0.08%), CD34+ count: 0.525X106/kg. On September 11, 2020, the donor peripheral blood was retransfused 201ml, MNC: 3.539X108/kg (0.1%), CD34+ count: 0.478X106/kg. On September 12, 2020, 322ml donor peripheral blood was transfused, MNC: 14.106X108/kg, CD34+ count: 2.5X106/kg. A total of 20.727X108/kg MNC and 3.503X106/kg CD34+ counts were infused over 3 days. The procedure was uneventful. Granulocyte engraftment was achieved on day 12 and platelet engraftment on day 11. After allo-HSCT, the patient was followed up to the time of publication. The general condition of the patient was good, most of the skin lesions on the left leg subsided, the bone marrow smear gradually returned to normal, and no abnormal phenotype cells were detected in MRD. Color Doppler ultrasound of superficial lymph nodes showed that the volume of enlarged lymph nodes in bilateral groin and bilateral axilla was significantly smaller than that before chemotherapy, and the number was reduced. 2 Discussion BPDCN is a malignant tumor in the blood system and is highly aggressive. Its "birthplace" is plasmacytoid dendritic cells (PDCS) [7] , which usually involve the skin, bone marrow, and lymph nodes, and have a poor prognosis. The clinical manifestations of BPDCN are diverse, and common symptoms include skin lesions, bone marrow involvement, and systemic spread. Skin lesions usually present as isolated or multiple masses, nodules, plaques, etc., while bone marrow involvement can lead to severe hematological abnormalities. According to the age distribution, the median age of onset of BPDCN ranged from 53 to 70 years. In terms of gender difference, the ratio of male to female shows a trend of (2.0-3.3)：1 [4,8] , and the incidence of male patients is higher. Most adults can respond to various chemotherapy regimens, but they are prone to relapse, and the treatment effect after relapse is not good, and their median overall survival is only 1 year [9] . This elderly male patient had a tendency to relapse after chemotherapy, and immediately achieved complete remission after sequential all-HSCT, and has not relapsed yet. However, because the follow-up time is not long, the evaluation of long-term efficacy needs further observation and follow-up. It is well known that the immunophenotype of BPDCN is usually positive for CD56, CD123, CD4 and TCL-1 [10] , and CD68 and CD1a can also be positive, but these markers lack specificity and need to be combined with molecular genetic testing to confirm the diagnosis. Studies have found that many BPDCN patients have TET2 gene mutations, and single-site mutations are common in the clonal proliferation stage, while multi-site mutations may mark disease progression to BPDCN, suggesting that mutation accumulation is related to disease development [11] . In addition, KRAS and BRAF mutations, MYB family gene abnormalities and MYC rearrangement are also found in some cases, which may be related to the pathogenesis [12-14] . Cytogenetic analysis shows that about two-thirds of BPDCN patients have complex chromosome karyotypes, and common recurrent abnormalities include 12p, 5q, 13q, 6q, 15q deletion and monosomy 9 [3, 15] . Its diagnosis depends on the combined analysis of flow cytometry and immunohistochemistry. Due to the high heterogeneity of immunophenotypes, it is necessary to integrate the results of clinical manifestations, imaging, morphology, molecular biology and immunophenotyping. BPDCN often involves skin, bone marrow and extramedullary sites (such as lymph nodes, central nervous system, lung, etc.). Positive markers (CD4, CD56, CD123, TCL1, etc.) and negative markers (CD3, CD19, MPO, etc.) should be used to distinguish BPDCN. For example, in the actual case, the pathological immunohistochemical results of the left inguinal lymph nodes of this patient showed that CD4, CD123 and CD56 were all positive at the time of initial diagnosis, which was consistent with the diagnostic criteria of BPDCN. The challenge in clinical diagnosis is that BPDCN mostly occurs in the skin and has non-specific manifestations, which is easily confused with skin diseases and myeloid sarcoma. Comprehensive examinations such as bone marrow cytology, pathology, flow cytometry [16] and imaging (such as PET-CT) should be performed at the first visit to ensure accurate diagnosis. In addition, it should be noted that in the study of BPDCN patients, on the one hand, it was found that some BPDCN patients could transform into acute myeloid leukemia or combined with myelodysplastic syndrome, and DNA methylation gene TET2 mutation was also detected in BPDCN patients. On the other hand, the demethylating agent AZA has been approved for intermediate-risk and high-risk myelodysplastic syndrome and acute myeloid leukemia. Based on these findings, we need to further explore the therapeutic effect of AZA on BPDCN [17] . In BPDCN, the Bcl-2 gene, which encodes an anti-apoptotic cell survival protein, was overexpressed. This situation provides an opportunity for the application of Bcl-2 inhibitors, which are targeted therapy drugs that have only been applied in clinical practice in recent years. Since BPDCN blast cells are sensitive to Bcl-2 inhibitor Venetoclax, and two cases of relapsed/refractory BPDCN patients have been reported to have a significant therapeutic effect by this drug, Venetoclax or other Bcl-2 inhibitors are recommended for the treatment of BPDCN patients [18] . This case of BPDCN has unique manifestations of CD4 and CD56 positivity, and there are various treatment options for BPDCN. Based on these two factors, AZA+GemOx regimen was used to provide the most appropriate treatment for the patient before allo-HSCT. GemOx regimen has a significant effect on a variety of cancer types, and is widely used in clinical practice, with controllable adverse reactions, and shows good synergistic effect in combination therapy. Therefore, in this case, the patient received combination therapy with azacitidine. However, the patient had a tendency to relapse after maintaining remission for a period of time. Since this disease is extremely dangerous, the patient was given all-HSCT consecutively, and then the patient regained remission, indicating that allogeneic hematopoietic stem cell transplantation has a better therapeutic effect on BPDCN, which will provide more direction and guidance for the clinical treatment of BPDCN. At present, there is no consensus on the maintenance treatment requirements and specific regimens for BPDCN patients after allo-HSCT. Chemotherapy combined with Venetoclax as a bridging method for allo-HSCT has been proved to significantly improve the prognosis of patients, and even achieve cure, which is the key part of the treatment. On this basis, to further reduce the risk of recurrence after transplantation, maintenance treatment with oral Venetoclax can be considered to improve the whole treatment process [19] . In addition, a small number of literatures have mentioned the role of donor lymphocyte infusion in the prevention and treatment of relapse after transplantation, but the results are quite different, so it has little reference value in clinical application [20-23] . It is worth noting that the left inguinal lymph node of this patient was positive for CD56, which led us to discuss the prognostic value of CD56 in this disease. In natural killer (NK) cells and some neuroendocrine tumor cells, the main expressed glycoprotein CD56, belongs to the immunoglobulin superfamily. CD56 is one of the indicators of poor prognosis in diseases such as acute myeloid leukemia and multiple myeloma. Moreover, CD56 is closely related to the progression and metastasis of a variety of malignant tumors, and has become a biomarker used in the diagnosis and treatment of many malignant tumors and prognosis evaluation [24] . Studies have shown that the expression of CD56 has an important impact on the function and anti-tumor ability of NK cells [25] . Some studies have suggested that CD56 is an independent indicator of poor prognosis in AML [26-27] . Studies have shown that the high expression of CD123 in BPDCN provides a new direction for targeted therapy. Therefore, CD123 CAR-T cell therapy came into being. The single-chain variable region fragment (scFV) of this therapy has high specificity and affinity, which can accurately recognize CD123 antigen on the surface of BPDCN blast cells, avoid reacting with normal blood or bone marrow cells, and achieve specific killing of tumor cells. As an important application of CAR-T therapy in the field of BPDCN, CD123 CAR-T has shown significant potential and become a powerful tool to overcome this refractory disease. Notably, studies have shown that such therapies may reduce the occurrence of cytokine release syndrome, a common adverse reaction of CAR-T therapy [28] , providing new ideas for optimizing the safety of immunotherapy. In addition, the treatment of BPDCN needs stratified management: for children and young patients, it is difficult to achieve sustained remission with chemotherapy alone, so hematopoietic stem cell transplantation becomes the core means to maintain long-term survival after the first complete remission. Older patients present a greater challenge, as they are often unable to tolerate intensive chemotherapy or transplantation. Although traditional low-intensity chemotherapy is one of the options, the breakthrough of targeted drugs in recent years has brought hope to this group. For example, CD123-targeting antibody drug Tagraxofusp (approved by the US FDA) has shown acceptable safety and efficacy in clinical practice by targeting CD123 molecule, and has become an important treatment option for elderly patients [29] . At present, there is no standard treatment for BPDCN, and chemotherapy is the main treatment. The commonly used chemotherapy regimens include those for lymphoma or acute leukemia. allo-HSCT is considered to be one of the effective ways to improve the prognosis, but there are individual differences in the efficacy. In recent years, a number of cutting-edge research results have clearly revealed that the pathogenesis of BPDCN is closely related to the mutation of epigenetic modifying genes and the abnormally high expression of methylation signals during transcription. Based on this, from the perspective of epigenetics, combined with gene targeting precision therapy strategy, it is hopeful to become a new treatment path with great potential and prospect. In this research trend, as the key means of epigenetic regulation, demethylation drugs, such as azacitidine and decitabine, have attracted extensive and in-depth attention and discussion in the academic field. Many research teams and scholars have carried out a full range of research on their mechanism of action, clinical efficacy and application prospects. 3 Summary BPDCN is a highly aggressive hematological malignancy, and its diagnosis and treatment require the integration of a variety of laboratory and clinical information. Although there is no unified treatment standard at present, chemotherapy, allogeneic hematopoietic stem cell transplantation, as well as emerging targeted and immunotherapy methods have provided certain curative effects for patients. Future studies should explore the molecular mechanism of BPDCN and develop individualized treatment strategies to improve the prognosis of patients. Declarations Funding This work was supported by the Science and Technology Program Of Binzhou Medical University (BY2017KJ34). Ethics Declaration This article has no ethical implications. Patient Consent to Publish declarations - Written informed consent for publication was obtained from the patient. - This report adheres to the CARE guidelines for case reports. Declaration of Interest: The authors declare that they have no conflicts of interest relevant to the manuscript. Clinical trial number : not applicable. Data Availability Statement ： All data supporting the findings of this study are available within the paper and its Supplementary Information. Ethics Statement This study was reviewed and approved by the The Research Ethics Committee of Binzhou Medical University Hospital. In accordance with the committee’s guidelines, all research procedures adhered to ethical standards for human participant research, including informed consent, confidentiality, and minimization of risks. References Joseph D K, Eric S, Oussama A, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: Myeloid and histiocytic/ dendritic neoplasms[J].Leukemia, 2022, 36(7): 1703–1719. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, 127(20): 2391–2405. Sweet K. Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment. Curr Opin Hematol, 2020, 27(2): 103–107. Deconinck E, Petrella T, Garnache Ottou F. Blastic plasmacytoid dendritic cell neoplasm: clinical presentation and diagnosis. Hematol Oncol Clin North Am, 2020, 34(3): 491–500. Garnache-Ottou F, Vidal C, Biichlé S, et al. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?. Blood Adv, 2019, 3(24): 4238–4251. Fay CJ, Iriarte C, Moslehi D, et al. Blastic plasmacytoid dendritic cell neoplasm mimicking dermatomyositis [ J ].JAAD Case Rep,2023,39:70-73. Sapienza MR, Abate f, Melle f, et al. Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target[J]. Haematologica, 2019, 104(4): 729–737. Venugopal S, Zhou S, El Jamal SM, et al. Blastic plasma⁃cytoid dendritic cell neoplasm⁃current insights [ J ]. Clin Lymphoma Myeloma Leuk, 2019, 19: 545⁃ 554. Garnache⁃Ottou F, Vidal C, Biichlé S, et al. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients [J]. Blood Adv, 2019, 3: 4238⁃ 4251. Beird HC, Khan M, Wang F, et al. Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Blood Cancer J, 2019, 9(12):99. Guan Jun, Zhou Ying, Wang Lanlan, et al. Clinical analysis of blastic plasmacytoid dendritic cell neoplasm [J]. Journal of Clinical Dermatology,2022,51(4):208-214. Sakamoto K, Takeuchi K. Cytogenetics of blastic plasmacytoid dendritic cell neoplasm: chromosomal rearrangements and DNA copy⁃number alterations [J]. Hematol Oncol Clin North Am, 2020, 34: 523⁃ 538. Li Junna, Ma Jiajia, Yu Jingwen, et al. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic analysis of 4 cases [J]. Journal of Diagnostic Pathology, 2024,31(3):199-202,207. DOI:10.3969/j.issn.1007-8096.2024.03.004. SAKAMOTOK,KATAYAMAR,ASAKAR,etal.Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm:association with immunoblastoid cytomorphology,MYC expression,and drug response[J].Leukemia,2018,32(12):2590-2603. Leroux D, Mugneret F, Callanan M, et al. CD4 +, CD56 + DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major largets: a study of 21 cases by the Groupe Francais de Cytogenetique Hématologique. Blood, 2002, 99(11) :4154-4159. Kerr D 2nd, Zhang L, Sokol L. Blastic Plasmacytoid Den⁃dritic Cell Neoplasm [J]. Curr Treat Options Oncol, 2019,20: 9. Khwaja R, Daly A, Wong M, et al. Azacitidine in the treat⁃ment of blastic plasmacytoid dendritic cell neoplasm: a report of 3 cases [ J ]. Leuk Lymphoma, 2016, 57:2720⁃ 2722. Montero J, Stephansky J, Cai T, et al. Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax [ J ]. Cancer Discov, 2017, 7:156⁃ 164. Cheng Ping, Wang Lanlan, Wang Qiuxiang, et al. Treatment of blastic plasmacytoid dendritic cell neoplasm with chemotherapy and Venetoclax bridging allogeneic hematopoietic stem cell transplantation [J]. Chinese Journal of Laboratory Hematology, 2023,31(05):1531-1536. DOI:10.19746/ j.cnki. issn1009 -2137. 2023. 05.044. Zhou Hong-sheng, XU Na, Sun Jing, et al. Allogeneic hematopoietic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm. Leukemia and Lymphoma,2012,21(11):659–662. Roos-Weil D, Dietrich S, Boumendil A, et al. Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood, 2013, 121(3): 440–446. Deotare U, Kim DD, Michelis FV, et al. Allogeneic hematopoietic stem cell transplantions in blastic plasmacytoid dendritic cell neoplasm in first complete remission: an effective therapy for a rare disease. Leuk Lymphoma, 2016, 57(8): 1942–1944. Steinberg A, Kansal R, Wong M, et al. Good clinical response in a rare aggressive hematopoietic neoplasm: plasmacytoid dendritic cell leukemia with no cutaneous lesions responding to 4 donor lymphocyte infusions following transplant. Case Rep Transplant, 2011, 2011: 651906. Liu YQ, Shen JZ, Awal IM, et al. CD56⁃positive diffuse large B⁃cell lymphoma / leukemia with BCL6 / MYC double⁃hit and multiple gene mutations: an indicator of poor prognosis [J]. J Int Med Res, 2020, 48: 300060520918087. Ana L Portillo, Eduardo A Rojas, Misaal Mehboob, etal. CD56 does not contribute to the antitumor, tissue homing, and glycolytic capacity of human NK cells, Journal of Leukocyte Biology, 2024;, qiae227. Sobas M, Montesinos P, Boluda B, et al. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all⁃trans retinoic acid and anthracycline⁃based regimens [ J]. Leuk Lymphoma,2019, 60: 1030⁃ 1035. Rai S, Singh S, Gupta R. Prognostic significance of CD56 and CD7 in acute myeloid leukaemia and their outcome [J].Am J Blood Res, 2020, 10: 109⁃ 117. Bôle⁃Richard E, Fredon M, Biichlé S, et al. CD28 / 4⁃ 1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm [J]. Leukemia, 2020, 34: 3228⁃ 3241. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic⁃Cell Neoplasm [ J]. N Engl J Med, 2019, 380: 1628⁃ 1637. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6975704","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":485013515,"identity":"0f0bfae6-1caf-409c-b308-07a794229c96","order_by":0,"name":"Cao Yuezhen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIie3RMUsDMRTA8RyBd0vw1pRC+xUiB4qcrV8l4cBuUhDkxisHmQS/gB8iq9sLN3QpdT3o0tsdLILgog1Z9a43OuQ/hvx4JI+QUOgfBpQiyuKaAY1W+4JQf8r7yFkMCveb20kSV5XYDCGThKW21XU6elxrPogAJQIlUGUapQurs+kloXbHyPyuh0iUDDxprF6cv5SQZ4zk9z3EPZ8zT3YHXUcG2cWYEVRlJ4lKlIJ7srS6vjGYfJ4gboyUwj3fauKIclPgBAFHULpPXlUct4vc1JBePYu8k0yfXj8OX98/bpVx+44P2cysq7Z5K+ad5I/8asTw+6FQKBT63RFFel577gqsIwAAAABJRU5ErkJggg==","orcid":"","institution":"Binzhou Medical University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Cao","middleName":"","lastName":"Yuezhen","suffix":""},{"id":485013516,"identity":"9ba7f36d-34c3-442d-9b5e-b8370aece9d0","order_by":1,"name":"Gao Na","email":"","orcid":"","institution":"Hospital of Binzhou Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gao","middleName":"","lastName":"Na","suffix":""},{"id":485013517,"identity":"d4b1ac60-41b6-4fd5-9873-39fb4968f29f","order_by":2,"name":"Gu Wenrong","email":"","orcid":"","institution":"Hospital of Binzhou Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gu","middleName":"","lastName":"Wenrong","suffix":""},{"id":485013518,"identity":"f1997575-c4cf-4d7d-84f9-3fad2d89d3da","order_by":3,"name":"Chu Wenhui","email":"","orcid":"","institution":"Hospital of Binzhou Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chu","middleName":"","lastName":"Wenhui","suffix":""},{"id":485013519,"identity":"fd437b94-4269-4311-8920-d21529d6bd43","order_by":4,"name":"Li Shuo","email":"","orcid":"","institution":"Hospital of Binzhou Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Shuo","suffix":""},{"id":485013520,"identity":"6e16b7cf-1ee6-48d9-90eb-ec76dad7b9ec","order_by":5,"name":"Wang Yang","email":"","orcid":"","institution":"Hospital of Binzhou Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-06-25 14:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6975704/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6975704/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87035931,"identity":"67426f9a-c664-44b8-beb8-79840f1cbf45","added_by":"auto","created_at":"2025-07-18 13:18:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":169014,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe skin of the lower leg at the beginning of the disease\u003c/strong\u003e：A front and B side: multiple infiltrative purplish red masses and nodules of different sizes, accompanied by local swelling and thickening and roughness of the skin, some of which were fused with each other and raised on the skin, with medium hard texture and slight tenderness.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/bd5c2920b91456d5c6cf9a5b.png"},{"id":87038214,"identity":"4c8d0a7c-7fd9-4476-add7-7759519019bd","added_by":"auto","created_at":"2025-07-18 13:26:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":516364,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin rash biopsy of the lower leg\u003c/strong\u003e: superficial skin tissue, no obvious changes in the epidermis, scattered mucin deposits in the papillary dermis, patchy and diffuse infiltration of lymphoid cells in the reticular layer, and atypia of lymphoid cells without epidermophilia. Pretibial myxedema or mucin deposition was not supported. Suspected lymphohematopoietic tumors.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/e926e26f1e30964c364ecd20.png"},{"id":87034687,"identity":"ab879ba1-e53c-483e-878e-468f8e90d694","added_by":"auto","created_at":"2025-07-18 13:10:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":551420,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePathological findings of the left inguinal lymph node\u003c/strong\u003e: the structure of the lymph node was destroyed, and the atypical lymphoid cells were diffusely distributed. The tumor cells were small to medium in size, with round or irregular nuclei, fine chromatin, inconspicuous nucleoli, and non-granular and non-abundant cytoplasm. Combined with histological and immunohistochemical results, relevant laboratory examinations and clinical history, it is highly suggested that BPDCN involves lymph nodes. It mainly differentiates myeloid leukemia and myeloid sarcoma. There is a great overlap between them in morphology and immunohistochemistry. Comprehensive analysis shows that BPDCN is more likely to be used. A1 immunohistochemistry: CD3 (-), CD20 (-), CD21 (weakly +), CD10 (-), Ki-67: the number of positive cells was about 80%, MPO (-), CD34 (-), TdT (-), CD117 (+), CD2 (+), CD43 (+), CD38 (+), ERG (+), CD68 (+), CD1 23 (+), CD15 (-), CD13 (scattered little +), CD56 (+), CD4 (+). EBV in situ hybridization was negative.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/8013b5df87cc3fb4330850d3.png"},{"id":87034692,"identity":"5b5385ab-58d5-4730-bfff-7eb70aa4b056","added_by":"auto","created_at":"2025-07-18 13:10:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":378113,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe result of Bone marrow biopsy\u003c/strong\u003e ：It showed that the proliferation of nucleated cells in bone marrow was active (about 55% hematopoietic capacity), and the granulocyte to red ratio was almost normal. Cells in all stages of granulocytes could be seen, mainly in the mature stage, and immature cells could be seen scattered. Cells in all stages of erythroid lineage could be seen, mainly middle and late erythroblasts. The number of megakaryocytes was generally normal, and the morphology of megakaryocytes was various, mainly lobulated. Reticular staining: there was no obvious reticular fiber proliferation in the bone marrow stroma. Immunohistochemistry: scattered and focal (+), CD20: scattered and focal (+), TDT: occasional (+), CD5: scattered and focal (+), CD10: scattered (+), CD23: occasional (+), Cyclin-D1: (-), ki-67\u0026lt;5%.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/f1d3c06f01620a19c86dace4.png"},{"id":87035934,"identity":"935dc600-435d-4af1-8473-c6622f76b9e3","added_by":"auto","created_at":"2025-07-18 13:18:48","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":353320,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePET-CT findings：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Enlarged lymph nodes in the left inguinal region (the larger one was about 3×1.7cm in size, FDG metabolism was increased, and SUVmax was about 4.6, which was consistent with the manifestations of lymph nodes involved by BPDCN combined with pathology in our hospital; 2. FDG uptake in multiple bones of the whole body was diffused increased, with a SUVmax of about 5.9, and the bone density of CT showed no definite abnormality. The subcutaneous tissue density was patchy in the middle and lower part of the left calf, and FDG metabolism was increased. Combined with pathology, the skin mucinosis was considered. (3) The slightly larger lymph nodes in level Ib and II of bilateral neck, increased FDG metabolism, and SUVmax was about 4.6, considering the possibility of reactive changes, reexamination was recommended to exclude BPDCN involvement; The hypodense lesions in the dental area with increased FDG metabolism (SUVmax 10.8) were considered as dental disease. 4. A few fibrous foci in both lungs, nodules in the upper lobe of the right lung, considering proliferative foci; 5, local FDG metabolism in the gastric wall of the cardia was increased, considering physiological or inflammatory uptake.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/cfd1bad85b8f55bb0b696b3f.png"},{"id":87034690,"identity":"9912d48e-6431-4671-9b75-2f86dff7e827","added_by":"auto","created_at":"2025-07-18 13:10:47","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":172400,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin of the lower leg after treatment\u003c/strong\u003e：The patient's calf mass gradually flattened and shrank after treatment with the hyper-CVAD A+B regimen.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/ea7ce00b5324e84b78019a0d.png"},{"id":87034706,"identity":"f354c3be-1b2b-436a-b601-da9b8ac1a0fc","added_by":"auto","created_at":"2025-07-18 13:10:48","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":116845,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin of the lower leg after treatment：\u003c/strong\u003eThe skin mass of the patient's left lower limb disappeared and the lesions subsided, with only a small amount of residual pigmentation.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/151cff2e141b160dc435c113.png"},{"id":87038876,"identity":"477bb399-04af-447f-b854-77c51b258594","added_by":"auto","created_at":"2025-07-18 13:34:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3214677,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6975704/v1/3839f87b-9351-4f10-b271-42d58c11a42d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Combination of chemotherapy and allogeneic hematopoietic stem cell transplantation for elderly patients with blastic plasmacytoid dendritic cell tumor: a case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBlastic plasmacytoid dendritic cell tumor, which originates from plasmacytoid dendritic cell precursor cells, is a very rare and aggressive hematological malignant disease. According to the WHO classification in 2016, BPDCN was classified as a malignant tumor of the lymphohematopoietic system\u003csup\u003e[1-3]\u003c/sup\u003e. BPDCN can involve multiple organs such as skin, central nervous system and bone marrow. In addition, it can also involve peripheral blood, lymph nodes, liver and spleen\u003csup\u003e[3-5]\u003c/sup\u003e. BPDCN is mostly treated in the department of hematology, but 90% of patients have skin lesions as the first manifestation\u003csup\u003e[6]\u003c/sup\u003e. Most of the first diagnosis departments are in the Department of dermatology, but due to its diversity of clinical manifestations, it is easy to be misdiagnosed and missed diagnosed. Therefore, the understanding level of the first diagnosis doctors in the department of dermatology is very important for the early detection, early diagnosis and early treatment of patients, so as to improve their survival cycle. As far as BPDCN tumor cells are concerned, they are often accompanied by epigenetic and cytogenetic abnormalities. However, there is no unified and effective treatment regimen. In view of the high malignant degree and poor prognosis of this disease, our department cooperated with Peking University People\u0026apos;s Hospital to treat an elderly patient with BPDCN. The patient was treated with chemotherapy followed by allogeneic hematopoietic stem cell transplantation. allo-HSCT). In this article, we will show and summarize the clinical features, genetic characteristics, diagnosis, treatment and prognosis of the patient, and also discuss the relevant literature of the disease in recent years.\u003c/p\u003e"},{"header":"1 Clinical data","content":"\u003cp\u003eThe patient was a 66-year-old man. The patient presented to our department on January 12, 2019 with a complaint of \u0026quot;skin plaque on the left calf for more than 6 months and a left groin mass for more than 10 days\u0026quot;. The skin plaque on the left calf (Fig 1), which was purple and accompanied by local swelling, thickening and roughness of the skin, and mild tenderness, appeared about 6 months ago without obvious causes. She presented with local swelling of the left groin and went to the outpatient department of Dermatology of our hospital for complete examination. The results of blood routine showed that: White blood cell (WBC) 3.4\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, red blood cell (RBC) 3.7\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L, hemoglobin(Hb) 129g/L, platelet (PLT) 197\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, lymphocyte 48.4%, neutrophil 24.8%; Local skin pathology(Fig 2): (lower leg) skin tissue examination showed that most of the epidermis was unchanged, with increased pigment in the basal layer, a large amount of mucoid material deposited in the dermal papilla and reticular layer, increased collagen in the deep layer, and chronic inflammatory cell infiltration. Mucinosis was considered, and lichen myxedematous could not be excluded. Inguinal color Doppler ultrasound showed multiple enlarged lymph nodes in the left inguinal region, the larger one was about 3.7cm\u0026times;1.8cm\u0026times;3.3cm, with clear boundaries, clear cortex and medulla, and thickened cortex. Ultrasound-guided needle biopsy of the left inguinal lymph nodes was performed, and the pathological results were back (Fig 3):For lymphoproliferative lesions, immuno- histochemical staining or consultation is recommended for further diagnosis, and the patient comes to our department for further diagnosis and treatment. Since the onset of the disease, the patient\u0026apos;s consciousness was clear, the spirit was good, the diet was good, the sleep was good, there was no obvious abnormality in urine and stool, and there was no significant change in weight recently.\u003c/p\u003e\n\u003cp\u003eThe patient had no history of hypertension, coronary heart disease, or diabetes. He had a history of tuberculosis infection and close contact, and his father died of tuberculosis. There was no history of drug allergy.\u003c/p\u003e\n\u003cp\u003ePhysical examination: T: 36.7℃, P: 79 times/min, R: 18 times/min, BP: 132/97 mmHg, conscious and active, local plaque was seen on the skin of the left calf, which was purple red, accompanied by local swelling and thickening and roughness of the skin. The diameter of the mass ranged from several millimeters to several centimeters. The mass was partially isolated and partially fused, slightly elevated on the skin. The left inguinal lymph node was palpable, about 4\u0026times;2\u0026times;3cm in size, leathery, well demarcated from the surrounding tissue, and mobile. The breath sounds were clear in both lungs, and no dry or wet rales were heard. The abdomen was soft, and the liver and spleen were not palpable subcostal.\u003c/p\u003e\n\u003cp\u003eThe results of routine blood test after admission showed white blood cell count 3.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, red blood cell count 3.6\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L, hemoglobin 120g/L, platelet count 193\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, and lymphocyte percentage 36.8%. Biochemical tests showed rheumatoid factor 61.79IU/ml, IgG 1690mg/dL, and IgA 519.1mg/dL. There were no obvious abnormalities in coagulation function and five tests of hepatitis B. Echocardiography showed that the left atrium was slightly enlarged and the LVEF was 67%. Plain CT scan of the chest and upper abdomen: 1. Double pneumonia, fibrous lesions, local thickening of bilateral pleura; 2. Right pulmonary nodule; 3. Aortic and coronary artery sclerosis; 4, gastric cardia gastric wall slightly thickened; 5. Enlarged retroperitoneal lymph nodes. Bone marrow cells showed active proliferation, granulocyte + oil +, G/E=2.21:1, granulocyte ratio was normal, the proportion of promyelocytes was 2.5%, and the morphology was normal. The proportion of erythrocytes was normal, mainly middle and late juvenile red, and the morphology was normal. The proportion of lymphocytes was decreased, and immature lymphoid cells could be seen without obvious abnormal morphology. The proportion of monocytes increased. Flow cytometry showed that no primitive/immature myeloid cells with abnormal immunophenotype were detected, and no obvious expression disorder of granulocytic differentiation was observed.\u003c/p\u003e\n\u003cp\u003eThe pathological results of bone marrow (posterior iliac) biopsy showed active hyperplasia of bone marrow with slightly increased T and B lymphocytes (Fig 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe PET-CT findings are shown in Figure 5（Fig 5）.\u003c/p\u003e\n\u003cp\u003eThe patient was diagnosed with BPDCN and received infusion port placement on 2024-1-17 and hyper-CVAD A chemotherapy on 2024-01-20 as follows: Cyclophosphamide 0.4g q12h d1-3, vincristine 2mg d4, 11, pirarubicin 60mg d4, dexamethasone 40mg d1-4, d11-14. On February 23, 2020, hyper-CVAD B regimen was given as follows: Methotrexate 2g d1, cytarabine 2g q12 d2-3, supplemented with calcium folinate rescue, hydration, alkalinization, antiemetic, acid suppression and stomach protection symptomatic and supportive treatment. During the period, delayed methotrexate metabolism and severe bone marrow suppression were observed, which gradually improved after comprehensive treatment. After two courses of chemotherapy, most of the mass in the left lower extremity flattened and decreased (Fig 6).\u003c/p\u003e\n\u003cp\u003eThe patient failed to receive sequential chemotherapy because of delayed methotrexate metabolism and severe bone marrow suppression after Hyper-CVAD chemotherapy. The patient was re-admitted to the hospital on 2024-04-15 for evaluation of bone marrow cells, and the morphology of bone marrow cells suggested that: The ratio of G/E was 4.23:1, and the ratio of promyelocytes and myeloblasts was 3%. The proportion of granulocytes and erythrocytes was normal, and the morphology was normal. The proportion of lymphocytes decreased and the morphology was normal. The proportion of monocytes in peripheral blood increased significantly (44%). In conclusion, considering the tendency of recurrence, the patient was changed to Azacitidine (AZA) +GemOx (AZA 100mg/d d1-7, gemcitabine 1.2g (1g/m2) d2+ oxaliplatin 120mg (100mg/m2) d2) regimen on 2024-04-16. After a course of chemotherapy with azacitidine +GemOx regimen, the patient\u0026apos;s condition was significantly improved. The multiple skin masses originally existing in the left calf completely disappeared, and most of the skin lesions also subsided, leaving only a small amount of pigmentation, and the treatment effect was remarkable (Fig 7). On physical examination, the left inguinal lymph nodes were significantly smaller than before.\u003c/p\u003e\n\u003cp\u003eThe patient was reexamined by color Doppler ultrasound of superficial lymph nodes on 2024-06-11: Bilateral axillary lymph nodes were enlarged (1.5\u0026times;0.7\u0026times;1.2cm on the left side and 1.6\u0026times;0.6\u0026times;1.6cm on the right side), and bilateral cervical lymph nodes were enlarged (1.5\u0026times;0.4\u0026times;0.8cm on the left side and 1.4\u0026times;0.4\u0026times;1.1cm on the right side). Bilateral inguinal lymph nodes were enlarged (3.6\u0026times;1.2\u0026times;2.5cm in the left and 3.3\u0026times;0.9\u0026times;2.0cm in the right; The results of routine blood test showed WBC 2.7\u0026times;10^9/L, RBC 2.8\u0026times;10^12/L, Hb 98g/L, PLT 128\u0026times;10^9/L, N% 15%. In summary, considering the recurrence of the primary disease, the patient was given azacitidine combined with GemOx regimen again on 2024-06-11.\u003c/p\u003e\n\u003cp\u003eDue to the extremely malignant degree and poor prognosis of BPDCN, the patient underwent haploidentical allo-HSCT from the son to the father in Peking University People\u0026apos;s Hospital after comprehensive consideration of the patient\u0026apos;s condition. The stem cells were derived from the peripheral blood stem cells of the donor (the patient\u0026apos;s son). The conditioning regimen was BU/CY+FLU+ATG+ CD25. On September 10, 2020, 321ml of donor peripheral blood was transfused, MNC: 3.082X108/kg (0.08%), CD34+ count: 0.525X106/kg. On September 11, 2020, the donor peripheral blood was retransfused 201ml, MNC: 3.539X108/kg (0.1%), CD34+ count: 0.478X106/kg. On September 12, 2020, 322ml donor peripheral blood was transfused, MNC: 14.106X108/kg, CD34+ count: 2.5X106/kg. A total of 20.727X108/kg MNC and 3.503X106/kg CD34+ counts were infused over 3 days. The procedure was uneventful. Granulocyte engraftment was achieved on day 12 and platelet engraftment on day 11.\u003c/p\u003e\n\u003cp\u003eAfter allo-HSCT, the patient was followed up to the time of publication. The general condition of the patient was good, most of the skin lesions on the left leg subsided, the bone marrow smear gradually returned to normal, and no abnormal phenotype cells were detected in MRD. Color Doppler ultrasound of superficial lymph nodes showed that the volume of enlarged lymph nodes in bilateral groin and bilateral axilla was significantly smaller than that before chemotherapy, and the number was reduced.\u003c/p\u003e"},{"header":"2 Discussion","content":"\u003cp\u003eBPDCN is a malignant tumor in the blood system and is highly aggressive. Its \u0026quot;birthplace\u0026quot; is plasmacytoid dendritic cells (PDCS)\u003csup\u003e[7]\u003c/sup\u003e, which usually involve the skin, bone marrow, and lymph nodes, and have a poor prognosis. The clinical manifestations of BPDCN are diverse, and common symptoms include skin lesions, bone marrow involvement, and systemic spread. Skin lesions usually present as isolated or multiple masses, nodules, plaques, etc., while bone marrow involvement can lead to severe hematological abnormalities. According to the age distribution, the median age of onset of BPDCN ranged from 53 to 70 years. In terms of gender difference, the ratio of male to female shows a trend of (2.0-3.3)：1\u003csup\u003e[4,8]\u003c/sup\u003e, and the incidence of male patients is higher. Most adults can respond to various chemotherapy regimens, but they are prone to relapse, and the treatment effect after relapse is not good, and their median overall survival is only 1 year\u003csup\u003e[9]\u003c/sup\u003e. This elderly male patient had a tendency to relapse after chemotherapy, and immediately achieved complete remission after sequential all-HSCT, and has not relapsed yet. However, because the follow-up time is not long, the evaluation of long-term efficacy needs further observation and follow-up.\u003c/p\u003e\n\u003cp\u003eIt is well known that the immunophenotype of BPDCN is usually positive for CD56, CD123, CD4 and TCL-1\u003csup\u003e[10]\u003c/sup\u003e, and CD68 and CD1a can also be positive, but these markers lack specificity and need to be combined with molecular genetic testing to confirm the diagnosis. Studies have found that many BPDCN patients have TET2 gene mutations, and single-site mutations are common in the clonal proliferation stage, while multi-site mutations may mark disease progression to BPDCN, suggesting that mutation accumulation is related to disease development\u003csup\u003e[11]\u003c/sup\u003e. In addition, KRAS and BRAF mutations, MYB family gene abnormalities and MYC rearrangement are also found in some cases, which may be related to the pathogenesis\u003csup\u003e[12-14]\u003c/sup\u003e. Cytogenetic analysis shows that about two-thirds of BPDCN patients have complex chromosome karyotypes, and common recurrent abnormalities include 12p, 5q, 13q, 6q, 15q deletion and monosomy 9\u003csup\u003e[3, 15]\u003c/sup\u003e. Its diagnosis depends on the combined analysis of flow cytometry and immunohistochemistry. Due to the high heterogeneity of immunophenotypes, it is necessary to integrate the results of clinical manifestations, imaging, morphology, molecular biology and immunophenotyping. BPDCN often involves skin, bone marrow and extramedullary sites (such as lymph nodes, central nervous system, lung, etc.). Positive markers (CD4, CD56, CD123, TCL1, etc.) and negative markers (CD3, CD19, MPO, etc.) should be used to distinguish BPDCN. For example, in the actual case, the pathological immunohistochemical results of the left inguinal lymph nodes of this patient showed that CD4, CD123 and CD56 were all positive at the time of initial diagnosis, which was consistent with the diagnostic criteria of BPDCN. The challenge in clinical diagnosis is that BPDCN mostly occurs in the skin and has non-specific manifestations, which is easily confused with skin diseases and myeloid sarcoma. Comprehensive examinations such as bone marrow cytology, pathology, flow cytometry \u003csup\u003e[16]\u0026nbsp;\u003c/sup\u003eand imaging (such as PET-CT) should be performed at the first visit to ensure accurate diagnosis.\u003c/p\u003e\n\u003cp\u003eIn addition, it should be noted that in the study of BPDCN patients, on the one hand, it was found that some BPDCN patients could transform into acute myeloid leukemia or combined with myelodysplastic syndrome, and DNA methylation gene TET2 mutation was also detected in BPDCN patients. On the other hand, the demethylating agent AZA has been approved for intermediate-risk and high-risk myelodysplastic syndrome and acute myeloid leukemia. Based on these findings, we need to further explore the therapeutic effect of AZA on BPDCN \u003csup\u003e[17]\u003c/sup\u003e. In BPDCN, the Bcl-2 gene, which encodes an anti-apoptotic cell survival protein, was overexpressed. This situation provides an opportunity for the application of Bcl-2 inhibitors, which are targeted therapy drugs that have only been applied in clinical practice in recent years. Since BPDCN blast cells are sensitive to Bcl-2 inhibitor Venetoclax, and two cases of relapsed/refractory BPDCN patients have been reported to have a significant therapeutic effect by this drug, Venetoclax or other Bcl-2 inhibitors are recommended for the treatment of BPDCN patients\u003csup\u003e[18]\u003c/sup\u003e. This case of BPDCN has unique manifestations of CD4 and CD56 positivity, and there are various treatment options for BPDCN. Based on these two factors, AZA+GemOx regimen was used to provide the most appropriate treatment for the patient before allo-HSCT. GemOx regimen has a significant effect on a variety of cancer types, and is widely used in clinical practice, with controllable adverse reactions, and shows good synergistic effect in combination therapy. Therefore, in this case, the patient received combination therapy with azacitidine. However, the patient had a tendency to relapse after maintaining remission for a period of time. Since this disease is extremely dangerous, the patient was given all-HSCT consecutively, and then the patient regained remission, indicating that allogeneic hematopoietic stem cell transplantation has a better therapeutic effect on BPDCN, which will provide more direction and guidance for the clinical treatment of BPDCN. At present, there is no consensus on the maintenance treatment requirements and specific regimens for BPDCN patients after allo-HSCT. Chemotherapy combined with Venetoclax as a bridging method for allo-HSCT has been proved to significantly improve the prognosis of patients, and even achieve cure, which is the key part of the treatment. On this basis, to further reduce the risk of recurrence after transplantation, maintenance treatment with oral Venetoclax can be considered to improve the whole treatment process\u003csup\u003e[19]\u003c/sup\u003e. In addition, a small number of literatures have mentioned the role of donor lymphocyte infusion in the prevention and treatment of relapse after transplantation, but the results are quite different, so it has little reference value in clinical application\u003csup\u003e[20-23]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIt is worth noting that the left inguinal lymph node of this patient was positive for CD56, which led us to discuss the prognostic value of CD56 in this disease. In natural killer (NK) cells and some neuroendocrine tumor cells, the main expressed glycoprotein CD56, belongs to the immunoglobulin superfamily. CD56 is one of the indicators of poor prognosis in diseases such as acute myeloid leukemia and multiple myeloma. Moreover, CD56 is closely related to the progression and metastasis of a variety of malignant tumors, and has become a biomarker used in the diagnosis and treatment of many malignant tumors and prognosis evaluation\u003csup\u003e[24]\u003c/sup\u003e. Studies have shown that the expression of CD56 has an important impact on the function and anti-tumor ability of NK cells\u003csup\u003e[25]\u003c/sup\u003e. Some studies have suggested that CD56 is an independent indicator of poor prognosis in AML\u003csup\u003e[26-27]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eStudies have shown that the high expression of CD123 in BPDCN provides a new direction for targeted therapy. Therefore, CD123 CAR-T cell therapy came into being. The single-chain variable region fragment (scFV) of this therapy has high specificity and affinity, which can accurately recognize CD123 antigen on the surface of BPDCN blast cells, avoid reacting with normal blood or bone marrow cells, and achieve specific killing of tumor cells. As an important application of CAR-T therapy in the field of BPDCN, CD123 CAR-T has shown significant potential and become a powerful tool to overcome this refractory disease. Notably, studies have shown that such therapies may reduce the occurrence of cytokine release syndrome, a common adverse reaction of CAR-T therapy\u003csup\u003e[28]\u003c/sup\u003e, providing new ideas for optimizing the safety of immunotherapy. In addition, the treatment of BPDCN needs stratified management: for children and young patients, it is difficult to achieve sustained remission with chemotherapy alone, so hematopoietic stem cell transplantation becomes the core means to maintain long-term survival after the first complete remission. Older patients present a greater challenge, as they are often unable to tolerate intensive chemotherapy or transplantation. Although traditional low-intensity chemotherapy is one of the options, the breakthrough of targeted drugs in recent years has brought hope to this group. For example, CD123-targeting antibody drug Tagraxofusp (approved by the US FDA) has shown acceptable safety and efficacy in clinical practice by targeting CD123 molecule, and has become an important treatment option for elderly patients\u003csup\u003e[29]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAt present, there is no standard treatment for BPDCN, and chemotherapy is the main treatment. The commonly used chemotherapy regimens include those for lymphoma or acute leukemia. allo-HSCT is considered to be one of the effective ways to improve the prognosis, but there are individual differences in the efficacy. In recent years, a number of cutting-edge research results have clearly revealed that the pathogenesis of BPDCN is closely related to the mutation of epigenetic modifying genes and the abnormally high expression of methylation signals during transcription. Based on this, from the perspective of epigenetics, combined with gene targeting precision therapy strategy, it is hopeful to become a new treatment path with great potential and prospect. In this research trend, as the key means of epigenetic regulation, demethylation drugs, such as azacitidine and decitabine, have attracted extensive and in-depth attention and discussion in the academic field. Many research teams and scholars have carried out a full range of research on their mechanism of action, clinical efficacy and application prospects.\u003c/p\u003e"},{"header":"3 Summary","content":"\u003cp\u003eBPDCN is a highly aggressive hematological malignancy, and its diagnosis and treatment require the integration of a variety of laboratory and clinical information. Although there is no unified treatment standard at present, chemotherapy, allogeneic hematopoietic stem cell transplantation, as well as emerging targeted and immunotherapy methods have provided certain curative effects for patients. Future studies should explore the molecular mechanism of BPDCN and develop individualized treatment strategies to improve the prognosis of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Science and Technology Program Of Binzhou Medical University (BY2017KJ34).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article has no ethical implications.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent to Publish declarations\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- Written informed consent for publication was obtained from the patient. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- This report adheres to the CARE guidelines for case reports. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest relevant to the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its Supplementary Information. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the The Research Ethics Committee of Binzhou Medical University Hospital. In accordance with the committee\u0026rsquo;s guidelines, all research procedures adhered to ethical standards for human participant research, including informed consent, confidentiality, and minimization of risks.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJoseph D K, Eric S, Oussama A, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: Myeloid and histiocytic/ dendritic neoplasms[J].Leukemia, 2022, 36(7): 1703\u0026ndash;1719.\u003c/li\u003e\n\u003cli\u003eArber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, 127(20): 2391\u0026ndash;2405.\u003c/li\u003e\n\u003cli\u003eSweet K. Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment. Curr Opin Hematol, 2020, 27(2): 103\u0026ndash;107.\u003c/li\u003e\n\u003cli\u003eDeconinck E, Petrella T, Garnache Ottou F. Blastic plasmacytoid dendritic cell neoplasm: clinical presentation and diagnosis. Hematol Oncol Clin North Am, 2020, 34(3): 491\u0026ndash;500.\u003c/li\u003e\n\u003cli\u003eGarnache-Ottou F, Vidal C, Biichl\u0026eacute; S, et al. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?. Blood Adv, 2019, 3(24): 4238\u0026ndash;4251.\u003c/li\u003e\n\u003cli\u003eFay CJ, Iriarte C, Moslehi D, et al. Blastic plasmacytoid dendritic cell neoplasm mimicking dermatomyositis [ J ].JAAD Case Rep,2023,39:70-73.\u003c/li\u003e\n\u003cli\u003eSapienza MR, Abate f, Melle f, et al. Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target[J]. Haematologica, 2019, 104(4): 729\u0026ndash;737.\u003c/li\u003e\n\u003cli\u003eVenugopal S, Zhou S, El Jamal SM, et al. Blastic plasma⁃cytoid dendritic cell neoplasm⁃current insights [ J ]. Clin Lymphoma Myeloma Leuk, 2019, 19: 545⁃ 554. \u003c/li\u003e\n\u003cli\u003eGarnache⁃Ottou F, Vidal C, Biichl\u0026eacute; S, et al. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients [J]. Blood Adv, 2019, 3: 4238⁃ 4251. \u003c/li\u003e\n\u003cli\u003eBeird HC, Khan M, Wang F, et al. Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Blood Cancer J, 2019, 9(12):99.\u003c/li\u003e\n\u003cli\u003eGuan Jun, Zhou Ying, Wang Lanlan, et al. Clinical analysis of blastic plasmacytoid dendritic cell neoplasm [J]. Journal of Clinical Dermatology,2022,51(4):208-214. \u003c/li\u003e\n\u003cli\u003eSakamoto K, Takeuchi K. Cytogenetics of blastic plasmacytoid dendritic cell neoplasm: chromosomal rearrangements and DNA copy⁃number alterations [J]. Hematol Oncol Clin North Am, 2020, 34: 523⁃ 538. \u003c/li\u003e\n\u003cli\u003eLi Junna, Ma Jiajia, Yu Jingwen, et al. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic analysis of 4 cases [J]. Journal of Diagnostic Pathology, 2024,31(3):199-202,207. DOI:10.3969/j.issn.1007-8096.2024.03.004.\u003c/li\u003e\n\u003cli\u003eSAKAMOTOK,KATAYAMAR,ASAKAR,etal.Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm:association with immunoblastoid cytomorphology,MYC expression,and drug response[J].Leukemia,2018,32(12):2590-2603.\u003c/li\u003e\n\u003cli\u003eLeroux D, Mugneret F, Callanan M, et al. CD4 +, CD56 + DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major largets: a study of 21 cases by the Groupe Francais de Cytogenetique H\u0026eacute;matologique. Blood, 2002, 99(11) :4154-4159.\u003c/li\u003e\n\u003cli\u003eKerr D 2nd, Zhang L, Sokol L. Blastic Plasmacytoid Den⁃dritic Cell Neoplasm [J]. Curr Treat Options Oncol, 2019,20: 9. \u003c/li\u003e\n\u003cli\u003eKhwaja R, Daly A, Wong M, et al. Azacitidine in the treat⁃ment of blastic plasmacytoid dendritic cell neoplasm: a report of 3 cases [ J ]. Leuk Lymphoma, 2016, 57:2720⁃ 2722. \u003c/li\u003e\n\u003cli\u003eMontero J, Stephansky J, Cai T, et al. Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax [ J ]. Cancer Discov, 2017, 7:156⁃ 164. \u003c/li\u003e\n\u003cli\u003eCheng Ping, Wang Lanlan, Wang Qiuxiang, et al. Treatment of blastic plasmacytoid dendritic cell neoplasm with chemotherapy and Venetoclax bridging allogeneic hematopoietic stem cell transplantation [J]. Chinese Journal of Laboratory Hematology, 2023,31(05):1531-1536. DOI:10.19746/ j.cnki. issn1009 -2137. 2023. 05.044.\u003c/li\u003e\n\u003cli\u003eZhou Hong-sheng, XU Na, Sun Jing, et al. Allogeneic hematopoietic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm. Leukemia and Lymphoma,2012,21(11):659\u0026ndash;662.\u003c/li\u003e\n\u003cli\u003eRoos-Weil D, Dietrich S, Boumendil A, et al. Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood, 2013, 121(3): 440\u0026ndash;446.\u003c/li\u003e\n\u003cli\u003eDeotare U, Kim DD, Michelis FV, et al. Allogeneic hematopoietic stem cell transplantions in blastic plasmacytoid dendritic cell neoplasm in first complete remission: an effective therapy for a rare disease. Leuk Lymphoma, 2016, 57(8): 1942\u0026ndash;1944.\u003c/li\u003e\n\u003cli\u003eSteinberg A, Kansal R, Wong M, et al. Good clinical response in a rare aggressive hematopoietic neoplasm: plasmacytoid dendritic cell leukemia with no cutaneous lesions responding to 4 donor lymphocyte infusions following transplant. Case Rep Transplant, 2011, 2011: 651906.\u003c/li\u003e\n\u003cli\u003eLiu YQ, Shen JZ, Awal IM, et al. CD56⁃positive diffuse large B⁃cell lymphoma / leukemia with BCL6 / MYC double⁃hit and multiple gene mutations: an indicator of poor prognosis [J]. J Int Med Res, 2020, 48: 300060520918087. \u003c/li\u003e\n\u003cli\u003eAna L Portillo, Eduardo A Rojas, Misaal Mehboob, etal. CD56 does not contribute to the antitumor, tissue homing, and glycolytic capacity of human NK cells, Journal of Leukocyte Biology, 2024;, qiae227.\u003c/li\u003e\n\u003cli\u003eSobas M, Montesinos P, Boluda B, et al. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all⁃trans retinoic acid and anthracycline⁃based regimens [ J]. Leuk Lymphoma,2019, 60: 1030⁃ 1035. \u003c/li\u003e\n\u003cli\u003eRai S, Singh S, Gupta R. Prognostic significance of CD56 and CD7 in acute myeloid leukaemia and their outcome [J].Am J Blood Res, 2020, 10: 109⁃ 117. \u003c/li\u003e\n\u003cli\u003eB\u0026ocirc;le⁃Richard E, Fredon M, Biichl\u0026eacute; S, et al. CD28 / 4⁃ 1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm [J]. Leukemia, 2020, 34: 3228⁃ 3241.\u003c/li\u003e\n\u003cli\u003ePemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic⁃Cell Neoplasm [ J]. N Engl J Med, 2019, 380: 1628⁃ 1637. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Blastic plasmacytoid dendritic cell neoplasm, BPDCN, Hematological malignancy, Old age, Chemotherapy, Allogeneic hematopoietic stem cell transplantation","lastPublishedDoi":"10.21203/rs.3.rs-6975704/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6975704/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly malignant hematological disease that is extremely rare in clinical practice, prone to recurrence, and has a very poor prognosis. Patients with this disease present with diverse clinical manifestations, including anemia, fever, bleeding, lymph node enlargement, and bone marrow invasion, which can easily lead to misdiagnosis as other hematological diseases. Other symptoms include skin lesions, cytopenia, bone marrow and lymph node or organ involvement. This disease often presents with skin manifestations as the first symptom, and the skin lesions are diverse, making it prone to missed diagnosis and misdiagnosis. The diagnosis of this disease usually requires a combination of clinical manifestations, imaging, histological features, and immunophenotype. Currently, there is no consensus on the first-line treatment for BPDCN. Our hospital admitted a 66-year-old male patient with the first manifestation of purple-red skin plaques and masses on the left lower extremity. The immunophenotype and histopathological characteristics were consistent with blastic plasmacytoid dendritic cell neoplasm. This report presents the therapeutic effect of chemotherapy bridging allogeneic hematopoietic stem cell transplantation in this patient and reviews relevant literature, hoping to enhance clinicians' understanding and awareness of this disease.\u003c/p\u003e","manuscriptTitle":"Combination of chemotherapy and allogeneic hematopoietic stem cell transplantation for elderly patients with blastic plasmacytoid dendritic cell tumor: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 13:10:43","doi":"10.21203/rs.3.rs-6975704/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-28T06:25:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-21T08:36:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-18T14:59:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317747439456932514774046074488911538989","date":"2025-08-11T03:11:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175972085365561758734955776384207967058","date":"2025-08-09T05:25:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-28T02:51:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-17T09:37:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"198638307872610060736853188252210482155","date":"2025-07-14T09:01:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232337513464281233580195153116981533264","date":"2025-07-14T06:16:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-14T05:18:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-07T07:41:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-06T11:28:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-05T16:37:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2025-07-05T16:34:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fdc7baed-5ece-4746-84e2-8bd39f0151e1","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-19T14:38:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-18 13:10:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6975704","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6975704","identity":"rs-6975704","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}