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1.
Armin G. Jegalian Nataliya P. Buxbaum Fabio Facchetti Mark Raffeld Stefania Pittaluga Alan S. Wayne Elaine S. Jaffe 《Haematologica》2010,95(11):1873-1879
Background
Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited.Design and Methods
This retrospective study analyzed the pathological and clinical findings of nine cases of blastic plasmactyoid dendritic cell neoplasm presenting in patients under the age of 18 years who were reviewed at our institution. We also identified 20 well-documented additional pediatric cases in the literature.Results
In the combined analysis, the overall survival rate among the 25 patients with available follow-up, all having received chemotherapy, was 72% (follow-up ranging from 9 months to 13 years, with a median of 30 months). The event-free survival rate was 64%. Nine patients were alive 5 years after the original diagnosis, although only three of them had undergone hematopoietic stem cell transplantation – one in first complete remission and two in second remission. Of the seven patients who lacked cutaneous disease at presentation, 100% survived, including five who were alive more than 5 years after diagnosis, although only two had undergone stem cell transplantation. Among the 18 patients who presented with cutaneous disease and for whom follow-up data were available, only 11 survived (61%). Detailed immunophenotypic characterization and clinical features of all cases are presented. Unexpectedly, three of four cases of blastic plasmacytoid dendritic cell neoplasm tested showed focal positivity for S-100. S-100 was negative in 28 cases of acute myeloid leukemia evaluated for this marker.Conclusions
In contrast to adult cases, in which long-term survival depends on stem cell transplantation in first complete remission, blastic plasmacytoid dendritic cell neoplasms in children are clinically less aggressive. Treatment with high-risk acute lymphoblastic leukemia-type chemotherapy appears to be effective, and stem cell transplantation may be reserved for children who relapse and achieve a second remission. Outcomes were more favorable in cases that lacked cutaneous disease at presentation, although a comparison of cutaneous and non-cutaneous cases might be confounded by differences in treatment regimens. Focal expression of S-100 may be seen in concert with other markers of plasmacytoid dendritic cells. 相似文献2.
H. J. Male M. B. Davis J. P. Mcguirk S. Abhyankar O. S. Aljitawi D. Zhang Siddhartha Ganguly 《International journal of hematology》2010,92(2):398-400
Blastic plasmacytoid dendritic cell (BPDC) neoplasm is a rare but clinically aggressive tumor known to be derived from the
precursors of plasmacytoid dendritic cells (CD123+) with a high frequency of cutaneous and bone marrow involvement. Though
majority of the patients initially respond to multi-agent chemotherapy, most would relapse within a year. We hereby report
a patient with disseminated cutaneous BPDC with marrow involvement diagnosed by typical histo-pathological and flow-cytometric
findings. He was subsequently treated with leukemia type induction regimen followed by allogeneic stem cell transplantation
in first complete remission. He is now 18 months posttransplantation with continued remission with full donor chimerism. We
recognize that BPDC with marrow involvement behaves like acute myeloid leukemia and aggressive treatment followed by stem
cell transplantation may lead to long-term remission in selected cases. 相似文献
3.
Fanny Angelot-Delettre Anne Roggy Arthur E. Frankel Baptiste Lamarthee Estelle Seilles Sabeha Biichle Bernard Royer Eric Deconinck Eric K. Rowinsky Christopher Brooks Valerie Bardet Blandine Benet Hind Bennani Zehaira Benseddik Agathe Debliquis Daniel Lusina Mikael Roussel Fran?oise Solly Michel Ticchioni Philippe Saas Francine Garnache-Ottou 《Haematologica》2015,100(2):223-230
Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor α chain (IL3-Rα or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401 were compared to those of several relevant cytotoxic agents. SL-401 exhibited a robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were observed at substantially lower concentrations than those achieved in clinical trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic cell neoplasm cell line and treated with a single cycle of SL-401 was significantly longer than that of untreated controls (median survival, 58 versus 17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic cell neoplasm cells are highly sensitive to SL-401, and support further evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic cell neoplasm. 相似文献
4.
母细胞性浆细胞样树突细胞肿瘤二例并文献复习 总被引:1,自引:0,他引:1
目的 提高对母细胞性浆细胞样树突细胞肿瘤(blastie plasmacytoid dendritic cell neoplasm,BPDC)的认识.方法 报道2例BPDC患者,并复习文献总结该病临床及实验窒检杏特点,介绍肿瘤细胞起源的最新进展.结果 2例患者均以皮肤结节起病,肿瘤细胞表达CD4和CD56,不表达髓系、T细胞以及B细胞特异性标志.对初始治疗敏感,但迅速复发,病程分别为26、11个月.结论 BPDC是少见的淋巴瘤亚型,具有独特的免疫表型,病程呈侵袭性,预后差.近期研究表明肿瘤细胞起源于浆细胞样树突细胞前体细胞. 相似文献
5.
Livio Pagano Caterina G. Valentini Sara Grammatico Alessandro Pulsoni 《British journal of haematology》2016,174(2):188-202
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematological malignancy derived from the precursors of plamacytoid dendritic cells, with an aggressive clinical course and high frequency of cutaneous and bone marrow involvement. Neoplastic cells express CD4, CD43 (also termed SPN), CD45RA and CD56 (also termed NCAM1), as well as the plasmacytoid dendritic cell‐associated antigens CD123 (also termed IL3RA), BDCA‐2 (also termed CD303, CLEC4E) TCL1 and CTLA1 (also termed GZMB). The median survival is only a few months as the tumour exhibits a progressive course despite initial response to chemotherapy. The best modality of treatment remains to be defined. Generally, patients receive acute leukaemia‐like induction, according to acute myeloid leukaemia (AML)‐type or acute lymphoid leukaemia (ALL)‐type regimens. The frequent neuromeningeal involvement indicates systematic pre‐emptive intrathecal chemotherapy in addition to intensive chemotherapy. Allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed in first remission, may improve the survival. Preliminary data suggest a potential role for immunomodulatory agents and novel targeted drugs. Herein epidemiology, clinical manifestations, diagnosis and management of BPDCN will be presented. In detail, this review focuses on the therapeutic aspects of BPDCN, proposing a treatment algorithm for the management of the disease, including induction chemotherapy, allogeneic HSCT and intrathecal prophylaxis at different steps of treatment, according to compliance, biological and clinical characteristics of patients. 相似文献
6.
Akane Suzuki Shori Abe Kaori Koyama Shinju Suzuki Munenori Nagao Masahiro Kobayashi Jun Nomura Tomomi Tsutsumi Tomoki Takeda Yumiko Oka Yuko Shirota Naruhiko Takasawa Takao Kodera Yoko Okitsu Shinichiro Takahashi Ryo Ichinohasama Junichi Kameoka 《Internal medicine (Tokyo, Japan)》2021,60(6):927
Spontaneous regression is rare in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). An 85-year-old man presented with pancytopenia and skin lesions, and the bone marrow exhibited 79.6% CD4+, CD56+, CD123+, and TCL-1+ abnormal cells, with a normal karyotype; he was thus diagnosed with BPDCN. While being followed without chemotherapy, he was admitted due to sepsis induced by Serratia marcescens, which was successfully treated with antibiotics. Notably, his blood cell counts improved, and the skin lesions disappeared. To our knowledge, this is the first reported case of spontaneous regression of BPDCN with a decrease in tumor cells in the bone marrow following sepsis. 相似文献
7.
Inoue D Maruyama K Aoki K Nagano S Maruoka H Imai Y Ito K Ishikawa T Takahashi T 《Acta haematologica》2011,126(2):122-128
Blastic plasmacytoid dendritic cell neoplasm (BPDCN), currently considered to originate from immature plasmacytoid dendritic cells (DC), is a rare and aggressive CD4+CD56+ neoplasm that frequently involves the skin and bone marrow. We present a case of an 80-year-old man with a CD4+CD56+ BPDCN that affected the orbital cavity and bone marrow. Although BPDCN has not been reported to express any lineage-specific markers, the neoplastic cells strongly expressed the CD13 antigen. Therefore, in addition to pathological examination, we attempted to induce in vitro morphological and surface marker changes with IL-3 and CD40 ligand. After treatment with these cytokines, the tumor cells enlarged markedly, acquired many fine dendrites, similar to mature DC, and showed enhanced expression of antigens specific to DC or antigen-presenting cells, such as CD40, CD80, CD83 and CD86. To the best of our knowledge, this is the first report of BPDCN expressing a myeloid antigen, CD13, although CD33 expression has been described in some cases. The present patient received 2 courses of combination chemotherapy consisting of cytarabine and etoposide, which resulted in complete remission. Given that the cellular origin of plasmacytoid DC is still controversial, myeloid antigen expression involving CD13 may not exclude a diagnosis of BPDCN. 相似文献
8.
Maiko Shimomura Takaki Asano Aya Furue Mizuka Miki Yasuhiko Sera Hiroshi Kawaguchi Kazuhiro Nakamura Masao Kobayashi 《Indian journal of hematology & blood transfusion》2016,32(1):26-31
Pediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that has an extremely poor prognosis despite the use of intensive chemotherapy. Recently, treatment of BPDCN with bone marrow transplantation (BMT) using myeloablative conditioning has been reported to increase survival in adults. We report a 9-year-old girl with cutaneous BPDCN who was successfully treated with combination chemotherapy followed by BMT using reduced intensity conditioning (RIC), without any adverse complications. The success of this treatment regimen suggests that BMT with RIC may be a feasible option for treating children with cutaneous BPDCN. 相似文献
9.
Figen Atalay Gül?en Tükenmez Demirci Dilek Bayramgürler Elif Birta? Ate?o?lu Semsi Y?ld?z 《Indian journal of hematology & blood transfusion》2015,31(2):302-306
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct and rare neoplastic entity and was classified as a subgroup of acute myeloblastic leukemia by the WHO in 2008. The median survival of patients was 15.2 months in a large case series. Allogeneic or autologous bone marrow transplantation has been recommended by some reports because of the disease’s poor prognosis. We present three patients who presented with both skin and bone marrow infiltration. A 57-year-old man, a 62-year-old woman, a 64-year-old man were admitted to our outpatient clinic because of skin lesions. All of the patient’s had bone marrow infiltration with positivity of the CD4, CD56, and CD123 staining. Survival of the patient’s were 42, 6 and 12 months, respectively. Two of the patients who presented as blastic form didn’t respond to any chemotherapy. BPDCN is a difficult disease to diagnosis and manage. CD4, CD56, CD123, CD303, and T cell leukemia/lymphoma 1. Cutaneous lesions can present as isolated nodules, macules, and disseminated macules and nodules. Positivities are crucial to the diagnosis of the disease in histological examination. Bone marrow infiltration or disease relapse at presentation were related to poor prognosis. Complete immunocytochemical staining must be performed for all patients who have cutaneous lesions with or without blood count abnormalities. Bone marrow (allogeneic or autologous) transplantation should be considered at the first remission. 相似文献
10.
Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10‐Color flow cytometry diagnosis and HyperCVAD therapy
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Uday Deotare Karen W.L. Yee Lisa W. Le Anna Porwit Anne Tierens Rumina Musani David Barth Emina Torlakovic Aaron Schimmer Andre C. Schuh Matthew Seftel Mark D. Minden Vikas Gupta Elizabeth Hyjek 《American journal of hematology》2016,91(3):283-286
Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four‐tube 10‐color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA‐DR, CD71. Seven patients received front‐line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo‐HCT). For a median follow up of 13.3 months, the 1‐year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10‐color FCM using a four‐tube AL panel demonstrating a characteristic pattern of antigen expression. Front‐line induction chemotherapy with HyperCVAD can yield high remission rates, but allo‐HCT is required for long‐term durable remissions. Am. J. Hematol. 91:283–286, 2016. © 2015 Wiley Periodicals, Inc. 相似文献
11.
12.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short. Allogeneic stem cell transplantation may improve the prognosis of BPDCN but the rate of relapse is still high. There are no specific targeted agents approved for patients with BPDCN, but advances in the understanding of the pathobiology of BPDCN and the results of early clinical studies have revealed novel targets and potentially effective agents. Novel targeted therapies may improve outcomes for patients with BPDCN in the future. 相似文献
13.
Fabio Facchetti Stefano A. Pileri Claudio Agostinelli Maria Paola Martelli Marco Paulli Adriano Venditti Massimo F Martelli Brunangelo Falini 《Haematologica》2009,94(2):285-288
Acute myeloid leukemia carrying cytoplasmic mutated nucleophosmin (NPMc+ AML) and blastic plasmacytoid dendritic cell neoplasm have been included as new entities in the 4th edition (2008) WHO classification of myeloid neoplasms. These conditions may show clinical and pathological overlapping features (leukemic and skin involvement, and expression of macrophage markers). In this study, we provide evidence that aberrant cytoplasmic dislocation of nucleophosmin – the immunohistochemical surrogate for NPM1 mutations – allows the two entities to be genetically separated. In fact, nucleophosmin is consistently cytoplasmic in NPMc+ AML (because of the presence of NPM1 mutations), whilst it is nucleus-restricted (predictive of a germline NPM1 gene) in blastic plasmacytoid dendritic cell neoplasm. Our results clearly point cytoplasmic nucleophosmin (a full predictor of NPM1 mutations) as a new marker for distinguishing NPMc+ AML and blastic plasmacytoid dendritic cell neoplasm, further clarify the cell of origin of NPMc+ AML, and justify the inclusion of these pathological conditions as separate entities in the new WHO classification. 相似文献
14.
Goto H Nishio M Endo T Sato N Koizumi K Fujimoto K Sakai T Kumano K Obara M Koike T 《European journal of haematology》2005,74(6):526-528
Abstract: Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5+ and CD20+ atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5+ primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month. 相似文献
15.
Raman Arora Ritesh Sachdev Tribhuwan Bind Md Ateek Khan 《Indian journal of hematology & blood transfusion》2013,29(3):171-172
Blastic plasmacytoid dendritic cell neoplasm is a recently classified aggressive hematodermic neoplasm derived from plasmacytoid dendritic cells. We describe two cases of this neoplasm, one a 15 year old child and other a 65 year male. The diagnosis was made by evaluating the detailed clinical history, morphology and flow cytometric findings. The diagnosis is rendered difficult owing to common morphological and flow cytometric overlaps. The neoplasms were characterized by skin and soft tissue involvement and strong CD4/CD56 positivity. These neoplasms are highly aggressive and have many diagnostic overlaps. Strong suspicion and detection will help in early therapeutic interventions. 相似文献
16.
17.
Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia? 总被引:5,自引:0,他引:5
E Vellenga W L van Putten M A Boogaerts S M Daenen G E Verhoef A Hagenbeek A R Jonkhoff P C Huijgens L F Verdonck J van der Lelie H C Schouten J Gmür P Wijermans A Gratwohl U Hess M F Fey B L?wenberg 《Bone marrow transplantation》1999,23(12):1279-1282
The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery. 相似文献
18.
Clinical and biologic features of CD4(+)CD56(+) malignancies 总被引:8,自引:2,他引:6
Feuillard J Jacob MC Valensi F Maynadié M Gressin R Chaperot L Arnoulet C Brignole-Baudouin F Drénou B Duchayne E Falkenrodt A Garand R Homolle E Husson B Kuhlein E Le Calvez G Sainty D Sotto MF Trimoreau F Béné MC 《Blood》2002,99(5):1556-1563
CD4(+)CD56(+) malignancies are rare hematologic neoplasms, which were recently shown to correspond to the so-called type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study presents the biologic and clinical features of a series of 23 such cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the absence of B, T, and myeloid lineage markers. Clinical presentation typically corresponded to cutaneous nodules associated with lymphadenopathy or spleen enlargement or both. Cytopenia was frequent. Circulating malignant cells were often detected. Massive bone marrow infiltration was seen in 20 of 23 (87%) patients. Most tumor cells exhibited nuclei with a lacy chromatin, a blastic aspect, large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, and cytoplasmic expansions resembling pseudopodia. Other immunophenotypic characteristics included both negative (CD16, CD57, CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA, CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in the absence of chemotherapy. Complete remission was obtained in 18 of 23 (78%) patients after polychemotherapy. Most patients had a relapse in less than 2 years, mainly in the bone marrow, skin, or central nervous system. Considering these clinical and biologic features, the conclusion is made that CD4(+)CD56(+) malignancies constitute a genuine homogeneous entity. Furthermore, some therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the CD4(+)CD56(+) malignant cell are discussed. 相似文献
19.
Oshimi K 《International journal of hematology》2002,76(Z2):118-121
Natural killer (NK) cells are lymphocytes with large granular lymphocyte morphology, CD3-CD56+ phenotype, non-MHC-restricted cytotoxicity, and germ-line configuration T-cell receptor genes. Two types of lymphomas originating from NK cells have been described; blastic NK-cell lymphoma, and nasal-type NK-cell lymphoma. Because recent reports indicate that blastic NK-cell lymphoma originates from the precursors of plasmacytoid dendritic cells, I will focus mainly on nasal-type NK-cell lymphoma, and discuss its pathogenesis, diagnostic problems, treatment strategy, and outcome. Nasal-type NK-cell lymphoma develops mostly in the nasal cavity and rarely in other sites, such as the skin and intestinal tract. Epstein-Barr virus (EBV) is found in lymphoma cells of almost all the patients, and is considered to be the etiologic agent. Indeed, EBV easily infects NK cells in the absence of CD21 antigen, or EBV receptor, on the surface of NK cells. Further, various types of oncogenes and suppressor oncogenes are found to be involved in its pathogenesis. Based on the data obtained from paraffin-embedded specimens, it is difficult to determine whether the lymphoma cells are of T-cell or NK-cell lineage, because immunohistochemical staining of cytoplasmic CD3 is positive both in T and NK cells, and CD56 is positive in a part of T cells. The presence of CD5 antigen indicates T-cell lineage. When the disease is limited, radiation therapy is effective, but not satisfactory. A new trial to use simultaneously both radiation and chemotherapy has started in Japan. In advanced stages, a combination chemotherapy including L-asparaginase seems to be promising, and high-dose chemotherapy with autologous or allogeneic stem cell support is under investigation. A recent report described the expression of short-length P-glycoprotein (P-gp), but not full-length P-gp in NK cells, and this mini-P-gp is unable to extrude daunorubicin. These findings may change the treatment strategy. Finally, I will present the results on interim analysis of 166 cases of nasal-type NK-cell lymphoma collected in Japan between 1994 and 1998. 相似文献
20.
Vriesendorp HM 《Experimental hematology》2003,31(10):844-854
Nuclear warfare research and treatment of radiation accident victims uncovered the potential of hemopoietic stem cell transplants. Prior to transplantation of hemopoietic stem cells patients receive "conditioning" agents: high-dose total-body irradiation and/or high-dose chemotherapy. High-dose conditioning causes at least 20% procedure-related mortality. Recent efforts to reduce procedure-related mortality by the use of low-dose conditioning included low-dose total-body irradiation, immunosuppressive agents, and the replacement of high-dose chemotherapy by donor lymphocytes for graft-vs-tumor effects. Procedure-related mortality remains high (10-30%). Tumor recurrence at 1 year is over 50%. In this review, the aims of conditioning (creation of space, prevention of hemopoietic stem cell rejection, eradication of immune memory, and eradication of tumor cells) are reexamined in those patient and animal studies that explore quantitative and mechanistic conditioning issues. Translational experimental animal models provide the best opportunities for the development of less toxic conditioning agents for human patients and require an analysis of the consequences of the effects of new conditioning agents on host-vs-graft as well as graft-vs-host reactions. Total-body irradiation or other forms of radiation create space, prevent rejection of histocompatible stem cells, and can eliminate immune memory to autoimmune antigens at modest, nontoxic doses. The transplantation of histoincompatible stem cells and the eradication of large loads of tumor cells remain problematic. The therapeutic index of allogeneic stem cell transplants will increase if new conditioning agents are targeted only to those host tissues that need conditioning: hemopoietic system, immune system, and tumor masses. Radiolabeled immunoglobulins are among the most promising new, low-toxicity conditioning agents. 相似文献