29:
76:(e.g. malignant plasmacytoid dendritic cell infiltrations into the skin to form single or multiple lesions) and/or leukemia (i.e. malignant plasmacytoid dendritic cells in blood and bone marrow). While commonly presenting with these clinical features, BPDCN, particularly in its more advanced stages, may also involve malignant plasmacytoid dendritic cell infiltrations in and thereby injury to the liver, spleen,
131:(47% of childhood cases but less often detected in adult cases). More advanced or severe cases may present with extreme organ and/or lymph node enlargements, skin lesions in virtually any site, and clinical evidence of malignant pDC infiltrations in the breasts, eyes, kidneys, lungs, gastrointestinal tract, bone, sinuses, ears, or testes. About 10% of individuals with BPDCN present with a
674:). The suspension was lifted in November 2017 after the trial used reduced amounts of the cells and with additional conditions were applied. A new phase 1 clinical trial is now recruiting 76 new patients to study the safety and efficacy of UCAR123 in treating BPDCN. The study began in June 2017 and is scheduled to end in December 2021.
159:, plasmacytic dendritic cells (pDC) and two types of conventional dendritic cells (cDC), myeloid cDC1 and myeloid cDC2. pDC circulate in the blood, representing <0.4% of all nucleated blood cells, and are present in various hematological tissues such as lymph nodes and spleen. Their major function is to detect and then initiate
1460:"Phase 1, Open-label Dose-escalation and Dose-expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of a Single Dose of UCART123 (Allogeneic Engineered T-cells Expressing Anti-CD123 Chimeric Antigen Receptor), Administered in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)"
693:
gene appears to be one of the most up-regulated (i.e. overactive) genes in BPDCN. Venetoclax inhibits the apoptosis-inhibiting action of BCL-2 and proved active in treating two patients with relapsed or refractory BPDCN. A phase I clinical trial testing the safety and efficacy of the drug in BPDCN is
127:, usually in the neck, due to malignant pDC infiltrations (~50% of cases); enlarged liver (~16% of cases) and/or spleen (26% of cases), also due to malignant pDC infiltrations; increased levels of malignant pDC in blood (i.e. >2% of nucleated cells) (~40% of cases), bone marrow (~65% of cases) and
633:
Due to the high rates of recurrence following initial therapy and the short overall survival times of individuals with BPDCN, prognosis of the disease is poor. However, further study of treatment regimens that include intrathecal chemotherapy and hematological stem cell transplantation in initial
545:
give complete remission rates of 77%, 93%, and 80%, respectively, in childhood PBDN and 47%, 77%, and 53%, respectively, in adult PBDN. However, these remissions were short-lived: post-treatment mean times to relapse or death were 12 months for children and 6.8 months for adults. Given these poor
1248:
Sumarriva Lezama L, Chisholm KM, Carneal E, Nagy A, Cascio MJ, Yan J, Chang CC, Cherry A, George TI, Ohgami RS (June 2018). "An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality".
1297:
Suma S, Sakata-Yanagimoto M, Nguyen TB, Hattori K, Sato T, Noguchi M, Nannya Y, Ogawa S, Watanabe R, Fujimoto M, Nakamura N, Kusakabe M, Nishikii H, Kato T, Chiba S (April 2018). "Blastic plasmacytoid dendritic cell neoplasm arising from clonal hematopoiesis".
593:
While few studies have reported on the treatment of BPDCN that has recurred following initial therapy, donor lymphocyte infusions coupled with alternative chemotherapy treatments have induced second complete or partial remissions in a few patients.
123:, bruise-like patches, and/or ulcers that most often occur on the head, face, and upper torso. The lesions are due to diffuse infiltrations of the skin by malignant pDC. In one large study, this presentation was accompanied by swollen
532:
There have been no controlled studies to define the optimal treatment for BPDCN. Studies on small numbers of individuals with the disease have found that the standard chemotherapy regimens used for the initial induction treatments of
447:. Such blast cells may also be observed in the circulation, bone marrow, or other tissues and suggest BPDCN. However, the diagnosis of this disease requires determination that these cells are pDC blast cells rather than AML,
84:, or other tissues. The neoplasm occurs in individuals of all ages but predominates in the elderly; in children, it afflicts males and females equally but in adults is far more common (~75% of cases) in males.
570:(i.e. taken from self) stem cells achieve better results, although one retrospective study in Japan found that autologous stem cells gave significantly better overall and progression-free survival rates. A
771:
Owczarczyk-Saczonek A, Sokołowska-Wojdyło M, Olszewska B, Malek M, Znajewska-Pander A, Kowalczyk A, Biernat W, Poniatowska-Broniek G, Knopińska-Posłuszny W, Kozielec Z, Nowicki R, Placek W (April 2018).
947:
Kim MJ, Nasr A, Kabir B, de
Nanassy J, Tang K, Menzies-Toman D, Johnston D, El Demellawy D (October 2017). "Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review".
57:
and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of
119:, but is more common in adults, particularly those between the ages 60–80. BPDCN usually (i.e. 61% to 90% of cases) presents with skin lesions, i.e. nodules, tumors, red or purple
1342:"Combination Chemotherapy (Methotrexate, L-asparaginase, Idarubicin and Dexamethasone) in Patients with Newly Diagnosed Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)"
455:(NKL) blast cells. Various studies have offered similar but not identical criteria to make this determination. All studies agree that pDC should have a typical plasmacytoid
662:
that directs them to attack and kill BPDCN cells. The intravenous infusion of these cells in patients with BPDCN is in phase 1 clinical trials but in
September 2017, the
713:"The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants"
147:
due to extensive malignant pDC infiltrations in the bone marrow. A leukemic phase of the disease is a common feature of end stage and post-therapy relapsing BPDCN.
407:
duplication or loss of entire chromosomes, particularly chromosomes 9, 13, or 15. Laboratory studies indicate that malignant pDC have a pathologically overactive
990:
Pemmaraju N (December 2017). "Novel
Pathways and Potential Therapeutic Strategies for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): CD123 and Beyond".
590:
followed by allogenic or autologous bone marrow transplantation in 26 participants newly diagnosed with BPDCN is planned but not yet in its recruiting phase.
315:
Blastic plasmacytoid dendritic cell neoplasm typically arises after the serial acquisition of multiple genetic abnormalities in pDC or their precursor cells.
605:(trade name Elzonris; formerly SL-401 and DT388-IL3) was approved in the United States in December 2018 for the treatment of BPDCN. Tagraxofusp-erzs is a
323:
gene are the most common genetic abnormality in the disease, occurring in 32–67% of all BPDCN cases and often accompanied by mutations in either the
1494:
107:
studies on treating BPDCN have therefore focused on non-chemotherapeutic regimens that target the molecular pathways which may promote the disease.
567:
563:
558:
following initial chemotherapy-induced remission also prolongs these remissions and, it is suggested, offers potential for curing the disease. (A
555:
1373:
Tandon, a.; Zhang, y.; Sokol, l. (2019). "Tagraxofusp, a novel CD123-directed cytotoxin to treat blastic plasmacytoid dendritic cell neoplasm".
1474:
1445:
1341:
415:) that stimulate their own proliferation. Presumably, these genetic abnormalities lead to the activation of the NF-κB pathway and/or other
546:
remission and survival rates, other treatments have been added to the initial treatment regimens. Studies have shown that the addition of
1420:
634:
treatment regimens (see previous section) and newer non-chemotherapeutic drug treatments (see next section) may improve this situation.
621:
to thereby gain entrance to the cells and then blocking these cells' protein synthesis (due to diphtheria toxin-mediated inhibition of
1097:
Wang S, Wang X, Liu M, Bai O (April 2018). "Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel agents".
431:
BPDCN is suggested by a biopsy of skin lesions which reveals the infiltration by medium-sized blast (i.e. immature) cells into the
524:
which are unique to AML, TCLL, or NKL blasts. Two other studies recommended assaying somewhat different sets of marker proteins.
622:
1475:"Phase 1 Study of Venetoclax, a BCL2 Antagonist, for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)"
1359:
538:
821:
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (May 2016).
663:
571:
452:
220:. Following detection of these intracellular pathogens, pCD initiate immune responses by producing massive amounts of
58:
547:
192:
91:
used to treat hematological malignancies. All too often, however, the disease rapidly recurs and does so in a more
667:
651:
559:
62:
232:(i.e. maturing) into conventional dendritic cells that further promote immune responses by, e.g. functioning as
233:
229:
96:
574:
clinical research study to test the safety and efficacy of a combination chemotherapy regimen consisting of
1459:
1355:
1200:
823:"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia"
618:
562:
may have contributed to the benefits seen after transplantation.) Studies have not yet determined whether
534:
479:
285:
104:
100:
81:
216:
206:
61:
rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the
1201:"Plasmacytoid pre-dendritic cells (pDC): from molecular pathways to function and disease association"
456:
257:
175:
88:
69:
class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.
659:
416:
347:
225:
128:
46:
1323:
1274:
1122:
1015:
972:
742:
467:. However, the studies disagree on which marker proteins to profile. One study's profile assayed
73:
28:
1398:
1390:
1315:
1266:
1225:
1176:
1114:
1066:
1007:
964:
910:
844:
803:
734:
221:
1382:
1307:
1258:
1215:
1166:
1158:
1106:
1056:
1046:
999:
956:
900:
892:
834:
793:
785:
724:
614:
602:
420:
140:
774:"Clinicopathologic retrospective analysis of blastic plasmacytoid dendritic cell neoplasms"
501:
483:
183:
160:
156:
92:
72:
Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy with features of
554:) as prophylaxis prolongs the period of CNS-free disease and increases overall survival.
1171:
1146:
905:
880:
798:
773:
606:
579:
464:
237:
66:
1488:
1199:
Alculumbre S, Raieli S, Hoffmann C, Chelbi R, Danlos FX, Soumelis V (February 2018).
1019:
729:
712:
610:
587:
268:
ability to differentiate into conventional dendritic cells when properly stimulated;
201:
164:
1327:
1278:
976:
746:
1386:
1126:
896:
575:
551:
486:, which are expressed on 80–100% of pDC but uncommon on AML, TCLL, or NKL blasts);
436:
187:
1220:
960:
839:
822:
319:(i.e. mutations which cause the gene to make no or a less active product) in the
460:
370:
77:
1311:
1110:
1003:
583:
293:
277:
144:
124:
50:
1394:
686:
444:
440:
331:
gene. Numerous other genetic abnormalities are associated with the disease:
273:
264:
production of large amounts of type I interferons when properly stimulated;
171:
167:
1402:
1319:
1270:
1229:
1180:
1118:
1070:
1061:
1011:
968:
914:
848:
807:
789:
738:
240:
plasmacytoid dendritic cells. They are distinguished from other dendritic,
115:
Blastic plasmacytoid dendritic cell neoplasm occurs in children, including
300:
failure to express certain marker proteins that are commonly expressed by
671:
647:
542:
505:
448:
412:
408:
316:
305:
245:
132:
54:
309:
301:
249:
241:
211:
116:
1262:
1162:
1051:
1034:
666:
suspended these because one patient developed a Grade 5 (i.e. lethal)
1446:"FDA Lifts Clinical Hold on Cellectis' UCART123 Trials in AML, BPDCN"
655:
494:
432:
387:
289:
136:
120:
617:. The fusion protein readily kills cultured pDC by binding to their
459:
and express a particular profile of marker proteins as detected by
103:. Consequently, BPDCN has a very low 5 year survival rate. Current
87:
Blastic plasmacytoid dendritic cell neoplasm typically responds to
682:
521:
517:
490:
419:
which promote the survival, proliferation, and/or other malignant
400:
396:
381:
375:
252:
types by exhibiting at least several of the following properties:
197:
1421:"FDA holds trials of Cellectis' cell therapy after patient death"
95:
form. Furthermore, the disease may occur in association with the
685:
is a cellular protein that can act to inhibit cell death due to
513:
509:
475:
281:
411:
pathway that promotes their survival and production of various
65:
designated BPDCN to be in its own separate category within the
471:
392:
179:
885:
Hematology. American
Society of Hematology. Education Program
435:
while sparing the epidermis. These cells exhibit irregular
135:-like disease, i.e. they exhibit circulating malignant pDC,
881:"Treatment of blastic plasmacytoid dendritic cell neoplasm"
1356:"FDA approves first treatment for rare blood disease"
236:. The malignant pDC in BPDCN have the appearance of
1033:Roberts I, Fordham NJ, Rao A, Bain BJ (July 2018).
550:administered drugs (administered directly into the
21:
1414:
1412:
1292:
1290:
1288:
1243:
1241:
1239:
1194:
1192:
1190:
1140:
1138:
1136:
1092:
1090:
1088:
1086:
1084:
1082:
1080:
942:
940:
938:
936:
934:
932:
930:
928:
926:
924:
874:
872:
870:
868:
866:
864:
862:
860:
858:
766:
764:
762:
760:
758:
756:
694:planned but not yet in its recruiting phase.
8:
1208:Seminars in Cell & Developmental Biology
43:Blastic plasmacytoid dendritic cell neoplasm
22:Blastic plasmacytoid dendritic cell neoplasm
362:locus on the long arm of chromosome 13, or
879:Sullivan JM, Rizzieri DA (December 2016).
27:
18:
1219:
1170:
1147:"Human dendritic cell subsets: an update"
1060:
1050:
904:
838:
797:
728:
358:locus on the short arm of chromosome 12,
49:. It was initially regarded as a form of
949:Journal of Pediatric Hematology/Oncology
354:locus on the short arm of chromosome 9,
703:
556:Hematopoietic stem cell transplantation
366:locus on the long arm of chromosome 5;
992:Current Hematologic Malignancy Reports
403:on the long arm of chromosome 19; and
399:on the long arm of chromosome 11 with
379:on the long arm of chromosome 11 with
7:
395:on the long arm of chromosome 8, or
391:on the short arm of chromosome with
1300:International Journal of Hematology
385:on the short arm of chromosome 10,
170:, particularly viruses such as the
778:Postepy Dermatologii I Alergologii
717:The British Journal of Dermatology
14:
1444:Melão, Alice (9 November 2017).
730:10.1111/j.1365-2133.2005.06905.x
423:in pDC and thereby cause BPDCN.
1495:Hematologic malignant neoplasms
1145:Collin M, Bigley V (May 2018).
672:UCART123#CAR-T cancer treatment
1387:10.1358/dot.2019.55.12.3058917
1039:British Journal of Haematology
897:10.1182/asheducation-2016.1.16
623:eukaryotic elongation factor 2
186:but also bacteria such as the
1:
497:which are unique to pDC; and
449:T-cell lymphoblastic lymphoma
1419:McKee, Selina (2017-09-05).
1360:Food and Drug Administration
1221:10.1016/j.semcdb.2018.02.014
961:10.1097/MPH.0000000000000964
840:10.1182/blood-2016-03-643544
566:(i.e. taken from others) or
560:graft-versus-leukemia effect
539:acute lymphoblastic leukemia
417:cellular activation pathways
59:plasmacytoid dendritic cells
1473:Lane, Andrew (6 May 2021).
711:Slater DN (November 2005).
664:Federal Drug Administration
453:aggressive NK-cell leukemia
1511:
228:interferons as well as by
193:Mycobacterium tuberculosis
1312:10.1007/s12185-018-2461-z
1111:10.1007/s00277-018-3259-z
1004:10.1007/s11899-017-0425-7
668:cytokine release syndrome
443:, and at least one small
155:There are three types of
63:World Health Organization
35:
26:
1381:(12). Portico: 735–742.
652:chimeric T cell receptor
234:antigen-presenting cells
97:myelodysplastic syndrome
790:10.5114/ada.2017.72269
480:Interleukin-3 receptor
317:Inactivating mutations
286:interleukin-3 receptor
272:the expression of key
210:and parasites such as
176:Herpes simplex viruses
105:translational research
101:acute myeloid leukemia
82:central nervous system
47:hematologic malignancy
658:engineered to bear a
654:-bearing cells, i.e.
613:(i.e. IL-3) fused to
217:Plasmodium falciparum
207:Aspergillus fumigatus
89:chemotherapy regimens
1362:. December 21, 2018.
1099:Annals of Hematology
1035:"Neonatal leukaemia"
53:-derived cutaneous
1425:www.pharmatimes.com
1344:. 19 November 2019.
660:monoclonal antibody
543:high-grade lymphoma
129:cerebrospinal fluid
36:CD4+ CD56+ lymphoma
74:cutaneous lymphoma
45:(BPDCN) is a rare
1358:(Press release).
1263:10.1111/his.13668
1163:10.1111/imm.12888
1052:10.1111/bjh.15246
421:phenotypic traits
352:CDKN2A-ARF-CDKN2B
184:hepatitis viruses
40:
39:
16:Medical condition
1502:
1479:
1478:
1470:
1464:
1463:
1456:
1450:
1449:
1441:
1435:
1434:
1432:
1431:
1416:
1407:
1406:
1370:
1364:
1363:
1352:
1346:
1345:
1338:
1332:
1331:
1294:
1283:
1282:
1245:
1234:
1233:
1223:
1205:
1196:
1185:
1184:
1174:
1142:
1131:
1130:
1094:
1075:
1074:
1064:
1054:
1030:
1024:
1023:
987:
981:
980:
944:
919:
918:
908:
876:
853:
852:
842:
833:(20): 2391–405.
818:
812:
811:
801:
768:
751:
750:
732:
708:
615:diphtheria toxin
603:Tagraxofusp-erzs
598:Tagraxofusp-erzs
161:immune responses
141:thrombocytopenia
99:or transform to
31:
19:
1510:
1509:
1505:
1504:
1503:
1501:
1500:
1499:
1485:
1484:
1483:
1482:
1472:
1471:
1467:
1462:. 29 July 2019.
1458:
1457:
1453:
1443:
1442:
1438:
1429:
1427:
1418:
1417:
1410:
1372:
1371:
1367:
1354:
1353:
1349:
1340:
1339:
1335:
1296:
1295:
1286:
1247:
1246:
1237:
1203:
1198:
1197:
1188:
1144:
1143:
1134:
1096:
1095:
1078:
1032:
1031:
1027:
989:
988:
984:
946:
945:
922:
878:
877:
856:
820:
819:
815:
770:
769:
754:
710:
709:
705:
700:
680:
645:
640:
631:
600:
530:
502:myeloperoxidase
429:
274:marker proteins
230:differentiating
157:dendritic cells
153:
151:Pathophysiology
113:
17:
12:
11:
5:
1508:
1506:
1498:
1497:
1487:
1486:
1481:
1480:
1465:
1451:
1436:
1408:
1375:Drugs of Today
1365:
1347:
1333:
1306:(4): 447–451.
1284:
1257:(5): 767–776.
1251:Histopathology
1235:
1186:
1132:
1105:(4): 563–572.
1076:
1045:(2): 170–184.
1025:
998:(6): 510–512.
982:
955:(7): 528–537.
920:
854:
813:
784:(2): 128–138.
752:
702:
701:
699:
696:
679:
676:
644:
641:
639:
636:
630:
627:
619:IL-3 receptors
609:consisting of
607:fusion protein
599:
596:
580:L-asparaginase
529:
526:
478:, CD123 (i.e.
465:flow cytometry
428:
425:
288:(i.e. CD123),
152:
149:
112:
109:
93:drug-resistant
38:
37:
33:
32:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1507:
1496:
1493:
1492:
1490:
1476:
1469:
1466:
1461:
1455:
1452:
1447:
1440:
1437:
1426:
1422:
1415:
1413:
1409:
1404:
1400:
1396:
1392:
1388:
1384:
1380:
1376:
1369:
1366:
1361:
1357:
1351:
1348:
1343:
1337:
1334:
1329:
1325:
1321:
1317:
1313:
1309:
1305:
1301:
1293:
1291:
1289:
1285:
1280:
1276:
1272:
1268:
1264:
1260:
1256:
1252:
1244:
1242:
1240:
1236:
1231:
1227:
1222:
1217:
1213:
1209:
1202:
1195:
1193:
1191:
1187:
1182:
1178:
1173:
1168:
1164:
1160:
1156:
1152:
1148:
1141:
1139:
1137:
1133:
1128:
1124:
1120:
1116:
1112:
1108:
1104:
1100:
1093:
1091:
1089:
1087:
1085:
1083:
1081:
1077:
1072:
1068:
1063:
1062:10044/1/59959
1058:
1053:
1048:
1044:
1040:
1036:
1029:
1026:
1021:
1017:
1013:
1009:
1005:
1001:
997:
993:
986:
983:
978:
974:
970:
966:
962:
958:
954:
950:
943:
941:
939:
937:
935:
933:
931:
929:
927:
925:
921:
916:
912:
907:
902:
898:
894:
890:
886:
882:
875:
873:
871:
869:
867:
865:
863:
861:
859:
855:
850:
846:
841:
836:
832:
828:
824:
817:
814:
809:
805:
800:
795:
791:
787:
783:
779:
775:
767:
765:
763:
761:
759:
757:
753:
748:
744:
740:
736:
731:
726:
723:(5): 874–80.
722:
718:
714:
707:
704:
697:
695:
692:
688:
684:
677:
675:
673:
669:
665:
661:
657:
656:T lymphocytes
653:
649:
642:
637:
635:
628:
626:
624:
620:
616:
612:
611:interleukin 3
608:
604:
597:
595:
591:
589:
588:dexamethasone
585:
581:
577:
573:
569:
565:
561:
557:
553:
549:
548:intrathecally
544:
540:
536:
527:
525:
523:
519:
515:
511:
507:
503:
500:
496:
492:
489:
485:
481:
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678:Venetoclax
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568:autologous
457:morphology
312:lineages.
294:Neuropilin
278:granzyme B
258:morphology
145:leukopenia
51:lymphocyte
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687:apoptosis
629:Prognosis
564:allogenic
528:Treatment
445:nucleolus
441:chromatin
427:Diagnosis
413:cytokines
348:deletions
214:-causing
204:-causing
190:-causing
174:-causing
172:cold sore
168:pathogens
143:, and/or
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638:Research
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246:lymphoid
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