H e m a t o lo g y E d u c a t io n - European Hematology Association

More documents

Recommendations

Info

References 1. Petersdorf EW, Malkki M, Gooley TA, Martin PJ, Guo Z. MHC haplotype matching for unrelated hematopoietic cell transplantation. PLoS Med. 2007;4(1):e8. 2. Ferrara GB, Bacigalupo A, Lamparelli T, Lanino E, Delfino L, Morabito A, et al. Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain. Blood. 2001;98(10):3150-5. 3. Kawase T, Morishima Y, Matsuo K, Kashiwase K, Inoko H, Saji H, et al. High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism. Blood. 2007;110(7): 2235-41. 4. Halter J, Kodera Y, Ispizua AU, Greinix HT, Schmitz N, Favre G, et al. Severe events in donors after allogeneic hematopoietic stem cell donation. Haematologica. 2009;94(1):94-101. 5. Cutler C, Li S, Ho VT, Koreth J, Alyea E, Soiffer RJ, et al. Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation. Blood. 2007;109(7): 3108-14. 6. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10(9):855-64. 7. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, Di Bartolomeo P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98(10):2942-7. 8. Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, et al. Thymoglobulin prevents chronic graftversus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006;12(5):560-5. 9. Byrne JL, Stainer C, Cull G, Haynes AP, Bessell EM, Hale G, et al. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transplant. 2000; 25(4):411-7. 10. Petersdorf EW, Anasetti C, Martin PJ, Gooley T, Radich J, Malkki M, et al. Limits of HLA mismatching in unrelated London, United Kingdom, June 9-12, 2011 hematopoietic cell transplantation. Blood. 2004;104(9): 2976-80. 11. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576-83. 12. La Nasa G, Caocci G, Argiolu F, Giardini C, Locatelli F, Vacca A, et al. Unrelated donor stem cell transplantation in adult patients with thalassemia. Bone Marrow Transplant. 2005; 36(11):971-975. 13. Crocchiolo R, Zino E, Vago L, Oneto R, Bruno B, Pollichieni S, et al. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation. Blood. 2009;114(7):1437-44. 14. Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 2010;116(14):2411-9. 15. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-9. 16. Ljungman P, Bregni M, Brune M, Cornelissen J, de Witte T, Dini G, et al. Allogeneic and autologous transplantation for haematological diseases, solid tumors and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010;45(2):219-34. 17. Lim Z, Brand R, Martino R, Van Biezen A, Finke J, Bacigalupo A, et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol. 2010; 28(3):405-11. 18. Ho VT, Kim HT, Aldridge J, Liney D, Kao G, Armand P, et al. Use of Matched Unrelated Donors Compared with Matched Related Donors Is Associated with Lower Relapse and Superior Progression-Free Survival after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2010. 19. Bacigalupo A, Socie’ G, Lanino E, Prete A, Locatelli F, Locasciulli A, et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party. Haematologica. 2010;95(6):976-82. 20. Eapen M, Logan BR, Confer DL, Haagenson M, Wagner JE, Weisdorf DJ, et al. Peripheral blood grafts from unrelated donors are associated with increased acute and chronic graftversus-host disease without improved survival. Biol Blood Marrow Transplant. 2007;13(12):1461-8. Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 55 |
V. Rocha Hôpital Saint Louis, Paris, France Hematology Education: the education program for the annual congress of the European Hematology Association 2011;5:56-63 Alternative donor stem cell sources Clinical results of unrelated cord blood transplantation Introduction UCBT has extended the availability of allogeneic hematopoietic stem cell transplantation (HSCT) to patients who would otherwise not be eligible for this curative approach. In comparison with other sources of allogeneic HSCT, UCB offers substantial advantages, 1 including: i) significantly faster availability of banked cryopreserved UCB units, with patients receiving UCBT in a median of 25–36 days earlier than those receiving an unrelated bone marrow graft; ii) extension of the donor pool due to tolerance of 1–2 HLA mismatches out of 6; iii) lower incidence and severity of acute graft-versushost disease (GvHD); iv) lower risk of transmitting infections by latent viruses such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV); v) lack of risk to the donor; vi) higher frequency of rare haplotypes compared with bone marrow registries, since it is easier to target ethnic minorities. However, the main problem of using UCB for transplantation is the relatively low number of hematopoietic progenitor (HPC) and stem cells (HSC) in UCB compared with bone marrow (BM) or mobilized peripheral blood (PB) grafts, which translates into an increased risk of graft failure, delayed hematopoietic engraftment 2,3,4,5,6 and delayed immune reconstitution. 7,8 The cumulative incidence of non-engraftment after UCBT varies from 10 to 20% and the median time to neutrophil recovery varies from 22 to 27 days. Many approaches have been investigated to enhance collection of HSC and HPC in cord blood units. Examples include injecting cord blood cells directly into the bone marrow; 9 in vivo or ex vivo amplification of cord blood cells; 10,11 use of double unit UCBT; 12,13 A B S T R A C T The use of umbilical unrelated cord blood (UCB) cells as an alternative source of hematopoietic cell transplantation has been widely used mainly for patients lacking an HLA-matched donor. UCB present many advantages over bone marrow or mobilized peripheral blood from volunteer donors, such as rapid availability, absence of risk for the donor, and decreased incidence of acute graft-versus-host disease. However, a significant clinical problem is delayed engraftment, and this is directly correlated with the number of hematopoietic stem cells in a cord blood unit. Currently many approaches have been investigated with the aim of improving the engraftment rate and decreasing transplantation related mortality, including the identification of prognostic factors associated with engraftment, the use of multiple donors, intrabone injection of UCB, ex vivo expansion, and co-transplantation with accessory cells. These approaches may increase the quality and availability of UCB for transplantation. use of reduced intensity conditioning (RIC) regimens; 1314,15 co-infusion with a haploidentical T cell depleted graft, 16,17 or mesenchymal stem cells (MSC). 18 Many prognostic studies for improving engraftment after UCBT have been performed, analyzing factors related to the patient, disease, donor, and transplantation. 5,19,20,21,22,23,24,25 Modifiable factors have been identified, such as HLA, cell dose, and others related to the graft choice or factors related to the conditioning regimen 26 or GvHD prophylaxis. 27 Challenges of cord blood transplantation Based on the initial experience the major challenges in UCBT are delayed engraftment, and graft rejection. In all clinical studies describing the outcome of UCBT, delayed engraftment and a high risk of graft failure have been described. Almost all series of UCBT in children and adults have demonstrated the profound impact of cell dose (measured as one or more of the numbers of total nucleated cells (TNC) prior to freezing or at infusion, colony-forming cells, and CD34 + cells) on engraftment, transplant-related events, and survival. 28 HLA matching was also recognized as an important factor for engraftment. In 1997, the Eurocord group described for the first time the association of TNC dose and HLA match with neutrophil and platelet recovery and survival, in 143 patients, mostly children, given related or unrelated cord blood transplantation. 19 In fact, the TNC dose infused (higher or lower than the median of 3.7x10 7 /kg) was the best predictive factor for | 56 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)
Page 1 and 2:
H e m a t o l o g y E d u c a t i o
Page 3 and 4:
Copyright Information ©2011 by Eur
Page 5 and 6:
Editorial Board Education Book Edit
Page 7 and 8:
Acute lymphoblastic leukemia 1-8 Th
Page 10 and 11:
S. Schnell P. Van Vlierberghe A. Fe
Page 12 and 13:
lineage cells, and in differentiati
Page 14 and 15: FLT3 mutations The FMS-like tyrosin
Page 16 and 17: 44. Bar-Eli M, Ahuja H, Foti A, Cli
Page 18 and 19: J.M. Rowe 1,2 C. Ganzel 1 1 Shaare
Page 20 and 21: treated on the MRC UKALL XII/ECOG29
Page 22 and 23: asparaginase (PEG), where the Esche
Page 24 and 25: or higher. It is, however, importan
Page 26 and 27: 25. Bruggemann M, Schrauder A, Raff
Page 28 and 29: lymphoblastic leukemia: prospective
Page 30 and 31: such as high white blood cell count
Page 32 and 33: doxorubicine, there was a trend tow
Page 34 and 35: of the aging process with respect t
Page 36 and 37: K.L. Rice 1 M. Buzzai 2 J. Altman 1
Page 38 and 39: ing FLT3-ITD, wild-type NPM1, or bo
Page 40 and 41: ciated with gene activation, via th
Page 42 and 43: leukemia with inv(16) and t(8;21):
Page 44 and 45: 99. Parsons DW, Jones S, Zhang X, e
Page 46 and 47: abnormalities, some of which are al
Page 48 and 49: file. 27,31 Thus, the double gene-m
Page 50 and 51: karyotype represents a distinct gen
Page 52 and 53: Table 1. Meta-analysis of 23 random
Page 54 and 55: A recent study by the Center for In
Page 56 and 57: Patients with HLA-matched related o
Page 58 and 59: After allogeneic HSCT, an autologou
Page 60 and 61: A. Bacigalupo Ospedale San Martino,
Page 62 and 63: Table 2. The effect of HLA mismatch
Page 66 and 67: neutrophil and platelet recovery an
Page 68 and 69: Figure 2. One Year-Overall Survival
Page 70 and 71: infused on day 21. No serious adver
Page 72 and 73: W, et al. Effect of graft source on
Page 74 and 75: TRM was higher for patients who rec
Page 76 and 77: following a myeloablative preparati
Page 78 and 79: effect. Surprisingly, none of the p
Page 80 and 81: nancies. Bone Marrow Transplant. 20
Page 82 and 83: J.G. Gilles Center for Molecular an
Page 84 and 85: 14C12 was humanized by grafting VH
Page 86 and 87: Table 1. VWD Classification. VWD Su
Page 88 and 89: Figure 1. Missense mutations found
Page 90 and 91: associated with an increased bleedi
Page 92 and 93: 49. Brown SA, Eldridge A, Collins P
Page 94 and 95: leed. These issues are especially i
Page 96 and 97: estored function. 43,44 A phase I t
Page 98 and 99: years’ experience of prophylactic
Page 100 and 101: J.A. Burger Department of Leukemia,
Page 102 and 103: chemotaxis, migration across vascul
Page 104 and 105: Regulatory T cells (T reg), identif
Page 106 and 107: 16. Burger JA, Ghia P, Rosenwald A,
Page 108 and 109: TE, Nowakowski GS, et al. CD49d exp
Page 110 and 111: andomized trial demonstrating impro
Page 112 and 113: Conclusions Chemoimmunotherapy has
Page 114 and 115:
with multiple comorbidities (≥ 2)
Page 116 and 117:
ment was finished in all 100 patien
Page 118 and 119:
Table 2. Treatment recommendation f
Page 120 and 121:
34. Ferrajoli A. The combination of
Page 122 and 123:
to be the source of additional gene
Page 124 and 125:
potential to prevent LSCs from acce
Page 126 and 127:
ABL1 confirms that eradication of d
Page 128 and 129:
65. Fiskus W, Pranpat M, Balasis M,
Page 130 and 131:
alive after 10 years. 11 Hence, CCy
Page 132 and 133:
each arm). A minimal change in myel
Page 134 and 135:
Any discussion about the definition
Page 136 and 137:
H. Kantarjian J. Cortes Leukemia De
Page 138 and 139:
59%; the CCyR rate was 44%. Among p
Page 140 and 141:
ern era of BCR-ABL1 tyrosine kinase
Page 142 and 143:
the hematopoietic system, 10 nor in
Page 144 and 145:
over the period of 6 weeks, demonst
Page 146 and 147:
Data on clonal changes in the blood
Page 148 and 149:
2006 Feb 1;107(3):924-30. 41. Liang
Page 150 and 151:
demonstrated that changes in osteob
Page 152 and 153:
“Mafia” transgenic mice in whic
Page 154 and 155:
68. Coetzee T, Fujita N, Dupree J,
Page 156 and 157:
ization. In WASP deficiency, lympho
Page 158 and 159:
Currently the epistatic relationshi
Page 160 and 161:
R. Küppers Institute of Cell Biolo
Page 162 and 163:
Figure 1. TNFAIP3 mutation in HL ce
Page 164 and 165:
Figure 2. HRS cells and their precu
Page 166 and 167:
Hansmann ML, et al. Detection of cl
Page 168 and 169:
fying patients for whom different a
Page 170 and 171:
prognosis HL, whilst those with res
Page 172 and 173:
12. Noordijk EM, Carde P, Dupouy N,
Page 174 and 175:
A. Sureda Consultant in Haematology
Page 176 and 177:
Figure 1. Long-term outcome of pati
Page 178 and 179:
from a MRD and 18 from MUDs. All pa
Page 180 and 181:
Parker PM, Stein AS, et al. High-do
Page 182 and 183:
R. Stasi Department of Haematology,
Page 184 and 185:
common variants in the regulatory r
Page 186 and 187:
against the TPO receptor (cMpl). 61
Page 188 and 189:
W.B. Mitchell A.A. Miller J.B. Buss
Page 190 and 191:
platelet counts and/or bleeding. Th
Page 192 and 193:
Mpl. Cell. 1994;77(7):1117-24. 6. d
Page 194 and 195:
ity and mortality associated with t
Page 196 and 197:
to azathioprine, and is particularl
Page 198 and 199:
stemming from antibodies against PE
Page 200 and 201:
L. Pasqualucci Institute for Cancer
Page 202 and 203:
cation of molecularly distinct subg
Page 204 and 205:
of cases) 46 and amplifications of
Page 206 and 207:
gene alterations in B cell lymphoma
Page 208 and 209:
W. Wilson National Cancer Institute
Page 210 and 211:
clear distinction among the lymphom
Page 212 and 213:
Treatment strategies in germinal ce
Page 214 and 215:
in ABC DLBCL (Hernandez et al., 201
Page 216 and 217:
DLBCL that mostly occurs in young p
Page 218 and 219:
phoma. J Clin Oncol. 2005;23:5347-5
Page 220 and 221:
Table 1. Diffuse Large B cell Lymph
Page 222 and 223:
sion/relapse are similar to those i
Page 224 and 225:
intensive therapy with curative int
Page 226 and 227:
A. Karsan Genome Sciences Centre an
Page 228 and 229:
Balanced translocations In contrast
Page 230 and 231:
some arm 5q have also been implicat
Page 232 and 233:
(H3K27) methyltransferase, and is a
Page 234 and 235:
38. Starczynowski DT, Morin R, McPh
Page 236 and 237:
G. Garcia-Manero Department of Leuk
Page 238 and 239:
trial evaluating different doses an
Page 240 and 241:
acid. 62 The second was a large mul
Page 242 and 243:
Borthakur G, et al. Cause of death
Page 244 and 245:
P. Krishnamurthy 1 G.J. Mufti 1,2 1
Page 246 and 247:
etween 1995 and 2005. 11 Five hundr
Page 248 and 249:
London, United Kingdom, June 9-12,
Page 250 and 251:
attainment of FDC post DLI. Interes
Page 252 and 253:
myelodysplastic syndromes is associ
Page 254 and 255:
ubiquitous chaperone that promotes
Page 256 and 257:
was thought that they are linked to
Page 258 and 259:
pathologic induction of miR-28 in M
Page 260 and 261:
STATs. Second, levels of HP1 alpha
Page 262 and 263:
72. Irandoust MI, Aarts LH, Roovers
Page 264 and 265:
A.M. Vannucchi Section of Hematolog
Page 266 and 267:
2,559 patients with a diagnosis of
Page 268 and 269:
tant use of aspirin should be caref
Page 270 and 271:
sions at this regard. Based on thes
Page 272 and 273:
in bcr-abl-negative myeloproliferat
Page 274 and 275:
Table 1. Prognostic scoring systems
Page 276 and 277:
Figure 1. Current inhibitors of JAK
Page 278 and 279:
Table 4. A risk-based approach to d
Page 280 and 281:
the flexibility to be adjusted as t
Page 282 and 283:
A. Vacca 1 D. Ribatti 2 1 Departmen
Page 284 and 285:
neovessel building together with MM
Page 286 and 287:
Mevastatin, a specific inhibitor of
Page 288 and 289:
egression of tumor vessels, and app
Page 290 and 291:
diagnosis does not require genetic
Page 292 and 293:
Genetics prognostic tools should be
Page 294 and 295:
sone induction improves outcome of
Page 296 and 297:
Table 1. Conventional chemotherapy
Page 298 and 299:
Novel agents given as consolidation
Page 300 and 301:
dence of peripheral neuropathy, gas
Page 302 and 303:
31. Barlogie B, Tricot G, Anaissie
Page 304 and 305:
Table 1. Major differences between
Page 306 and 307:
first line therapy have shown survi
Page 308 and 309:
transplantation, 7,91 and generally
Page 310 and 311:
methylation characterizes juvenile
Page 312 and 313:
Table 1. Clinical signs of possible
Page 314 and 315:
Table 4. Distribution of CSF involv
Page 316 and 317:
ently results in a less than 5% cum
Page 318 and 319:
90. German-Austrian-Swiss ALL-BFM S
Page 320 and 321:
U. Nowak-Göttl 1 R. Junker 1 A. Kr
Page 322 and 323:
Based on the data obtained from the
Page 324 and 325:
59. Male C, Chait P, Ginsberg JS, e
Page 326 and 327:
Table 1. Characteristic features of
Page 328 and 329:
Table 2. Mutational spectrum of CDA
Page 330 and 331:
megarakaryoblastic leukemia (AMKL)
Page 332 and 333:
R.E. Ware Professor and Vice-Chairm
Page 334 and 335:
protein, cytokines, and soluble adh
Page 336 and 337:
example, improving blood viscosity
Page 338 and 339:
92(9):1266-7. 36. Bensinger TA, Gil
Page 340 and 341:
London, United Kingdom, June 9-12,
Page 342 and 343:
port have also been used. 5 Combina
Page 344 and 345:
Wingard JR, Young J-AH, Boeckh MJ.
Page 346 and 347:
K. Rezvani 1 J. Barrett 2 1 Haemato
Page 348 and 349:
include the childhood infectious il
Page 350 and 351:
Summary Patients undergoing hematop
Page 352 and 353:
Table 1. Key issues. In a retrospec
Page 354 and 355:
invasive method to assess iron over
Page 356 and 357:
stitution but even with optimal sub
Page 358 and 359:
T.M. Hackeng Department of Biochemi
Page 360 and 361:
and inhibits FVIIa, and that the se
Page 362 and 363:
Figure 4. Regulation of coagulation
Page 364 and 365:
T. Baglin Department of Haematology
Page 366 and 367:
Figure 1. Illustration of alternati
Page 368 and 369:
compared with 3.5% in patients with
Page 370 and 371:
49. Hron G, Kollars M, Binder BR, E
Page 372 and 373:
Women receiving vitamin K antagonis
Page 374 and 375:
molecular weight heparin as prophyl
Page 376 and 377:
eral morbidity and mortality. 17-21
Page 378 and 379:
the HOD construct. Furthermore, the
Page 380 and 381:
Goals of future murine studies incl
Page 382 and 383:
F. Noizat-Pirenne C. Tournamille Et
Page 384 and 385:
phenotype. 26 In 2010, we investiga
Page 386 and 387:
ody has been involved in DHTR. 37 T
Page 388 and 389:
antigen. Cases can be encountered d
Page 390 and 391:
S.R. Sloan Harvard Medical School &
Page 392 and 393:
We also analyzed patient databases
Page 394 and 395:
Index of authors Altman J. 27 Bacig
Page 396 and 397:
Cornelissen J. Affiliations to disc
Page 398 and 399:
GlaxoSmithKline (Research Support;
show all

H e m a t o lo g y E d u c a t io n - European Hematology Association

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?