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

More documents

Recommendations

Info

include the childhood infectious illnesses (measles, mumps, rubella, diphtheria) polio, pertussis, tetanus, hepatitis A and B, and influenza. Immunity to these agents is conferred by lifelong production of protective antibodies. Immunity to some agents like tetanus is not permanent and may require vaccine boosts. The rationale for vaccinating SCT recipients is the observation that in the decade after transplant, antibody levels to many of these agents decline without further boosting. Internationally agreed guidelines drawn up by European and American stem cell transplantation groups, the Infectious Disease Society of America and the Center for Disease Control recommend revaccination of all SCT recipients within 2 years of transplant with a full reimmunization schedule, as well as yearly influenza vaccine. 7 While this is a very reasonable strategy, it is of interest to note that the risk of developing new infections from childhood exanthems appears to be extremely rare in post SCT recipients even when not vaccinated. 3 However, it is anticipated that as more transplants using immunologically naïve umbilical cord blood are performed, the risk of new infection from some of these agents will increase. Influenza virus SCT recipients remain at particular risk from severe and overwhelming infection with influenza virus for many months after SCT. The variability in influenza strains requires yearly administration of vaccine for the prevalent strain and it is therefore appropriate to vaccinate all SCT recipients yearly (avoiding intranasal live virus vaccines) to prevent seasonal flu. 8 Patients undergoing all forms of SCT (autologous and allogeneic) are at risk from influenza and may not mount functional protective immunity when vaccinated after transplant. 9 The recent outbreak of new pandemic strain A/H1N1 stressed the importance of having strategies in place for management of these patients. When the new pandemic H1N1 strain spread rapidly around the world, new vaccines were rapidly developed. Very little was known about the safety, immunogenicity, and optimal dosing regimen of 2009 H1N1 vaccine in the immunocompromised host, although several investigators reported efficacy of single dosing in healthy adults and children. 10–13 A number of studies, including work by our group, demonstrated that vaccination against 2009 pandemic H1N1 is associated with an acceptable safety profile in SCT recipients. 14–16 We found that the immune response in allogeneic SCT recipients can be substantially improved by a second dose of vaccine, supporting the European Medicines Agency and the UK DoH guidelines for the administration of two vaccine doses in this group of patients. 14 These data may also apply to vaccination against other viral agents in the immunocompromised host and warrant further studies. Hepatitis B Whether transmitted from donor to recipient, reactivating in the recipient, or occurring de-novo, represents an important post-transplant problem because of the propensity of Hep B to cause liver damage. Patients who are Hep B surface and core antigen positive require lamivudine antiviral treatment post SCT. Negative seroconversion – the loss of protective antibody to Hep B – is an indication to revaccinate. 17,18 London, United Kingdom, June 9-12, 2011 Tetanus Antibodies to tetanus fall after SCT. Revaccination 1year post SCT is partially effective but immunity may decline within a year. 19 Immunity to capsulated bacteria 20,21 Since immunity to capsulated bacteria pneumococcus, haemophilus influenzae type B (HIB) and to a lesser extent, meningococcus depends on circulating antibodies, SCT recipients with defective antibody production are particularly at risk from these infections. Notably patients who have been splenectomized and those with chronic GVHD are especially vulnerable. The problem with pneumococcal vaccines has been the incomplete coverage of all the common antigenic strains of the bacteria. However, the replacement of the earlier 7-valent vaccine (PCV7; Prevnar) by a 13-valent vaccine (Prevnar13), (both Pfizer Inc) is likely to provide more effective protection against pneumococcus in the SCT recipients. Despite the lack of data, the 13-valent vaccine is recommended for use in SCT patients until additional studies have been performed. A clinical trial to assess the efficacy of this 13-valent vaccine in allogeneic SCT recipients is ongoing. Immunity to DNA viruses after SCT The DNA viruses CMV, HSV, VZV, EBV, Adenovirus (ADV) BKV, and human papillomavirus (HPV), represent a group of viruses that can reside in the recipient lifelong after primary infection. These viruses generate protective immunity in the immune competent host but can reactivate if immune function falls off, as occurs after SCT. The reactivation of these viruses in an immune compromised host is potentially life-threatening. Unlike the previous categories of infectious agents, immunity is largely cell mediated, and commercial vaccines have not been developed against these viruses. Fortunately, the antiviral agents, acyclovir, ganciclovir, foscarnet, and cidofovir have activity against HSV, VZV, and CMV. Cidofovir has some efficacy against the BK virus and adenovirus. Furthermore, effective adoptive transfer of viral specific T cells can effectively control adenovirus, EBV, and CMV and rituximab can control EBV-related lymphoproliferative disease. 22–24 Two exceptions in this category are VZV and HPV, where effective vaccines exist and are being evaluated in SCT recipients. VZV Reactivation of VZV in the form of herpes zoster is a very frequent problem after SCT and while it can be suppressed with continuous treatment with acyclovir or valacyclovir, the virus typically reactivates promptly after discontinuation of antivirals. 25 A VZV vaccine represents a cheaper and more durable alternative to preventing zoster. However, vaccination of recipients with repeated doses of live, attenuated VZV vaccine is only partially protective. 26 An alternative approach is to vaccinate the donor. Limited studies suggest this approach may be at least partially protective in the recipient. 27 Two new inactivated varicella vaccines are under development. Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 339 |
16 th Congress of the European Hematology Association HPV Squamous cell cancers (SCC) involving the head and neck and cervix are increased after allogeneic SCT and in immunosuppressed individuals. Among SCT recipients, this risk is five times higher in patients with a history of chronic GVHD, and in a recent study, patients receiving immunosuppression for more than 3 years post SCT had the greatest risk of cervical dysplasia. 28 SCC are linked to HPV infection – especially HPV strains 16 and 18 – and HPV vaccination is now approved for prevention SCC and HPV warts in both healthy males and females. Vaccination results in over 99% seroconversion in healthy individuals and is around 95% in immunosuppressed individuals. These observations provide a strong rationale to give HPV vaccine to post transplant recipients to reduce the risk of SCC. 29 Several trials are currently evaluating the HPV strain 6,11,16,18 vaccine given in three doses starting 3– 12 months post SCT. Standard guidelines for vaccination Collaboration between European, North, and South American groups has produced unified global guidelines for transplant centers. 3,7,30 Their recommendations are summarized (Table 2). New developments Improving post transplant immune competence A clearer understanding of the dynamics of immune recovery post SCT and the cytokines that control lymphocyte recovery reveals several strategies that could be used to improve immune responses to vaccines. The first few weeks after SCT represent a period of powerful lymphoproliferative stimuli driven by IL-15 and IL-7 in particular, and promoting T cell recovery. Lymphocytes stimulated by vaccine at this stage post SCT expand preferentially. It may, therefore, be possible to rapidly induce immunity to infectious agents by early vaccination after SCT. Vaccine responses might be further enhanced by treatment with IL-15 or IL-7, which will soon be available for clinical trials. Another strategy being explored is the use of denileukin difitoxin (Ontak ©), which targets the CD25 IL-2 receptor and can be used to block CD4+ CD25+ FoxP3+ regulatory T cells to enhance antigen-specific proliferation. 31 However, immunostimulatory strategies will need to be applied cautiously in allogeneic SCT because of the risk of inducing GVHD. Vaccinating the patient pre-transplant Patients with multiple myeloma are severely immunecompromised and fail to make antibody responses to common vaccines. 32 Autologous SCT only worsens the patient’s already compromised immune system and increases the risk of post transplant infection. Influenza can be fatal in these patients, and post transplant vaccination is not always protective. A recent study showed that immunity to influenza in myeloma ASCT recipients can be significantly improved by adoptive transfer of T cells, previously stimulated by pre-transplantation multivalent flu vaccine, followed by a vaccine boost 2 weeks later. 33 This strategy of combining pre-and post transplant vaccination boosting with reinfusion of vaccineprimed lymphocytes could be more generally applied to boost immunity to a variety of infective agents or tumor antigens before autologous SCT. Tumor vaccines As our ability improves to control infectious problems and other transplant-related complications after SCT, the problem of relapse of malignant disease becomes an increasingly significant cause of post transplant treatment failure. Lessons learned in protecting patients with vaccines against infectious agents have relevance for developing effective tumor vaccines. There is currently only limited experience combining anti-tumor vaccines with SCT but combination of leukemia-specific vaccines with SCT promises to increase the immune competence of the graft to control and eradicate residual malignant disease. 34 Table 2. Post transplant vaccine schedule drawn up by an international consortium (adapted from 3,7 ). Vaccine Recommendation* Time post-SCT Doses Comments Non living vaccines Pneumococcal conjugate + 3–6 months 3-4 Tetanus Diphtheria Pertussis + 6–12 months 3 D T response improved if donor is vaccinated H Influenzae conjugate + 6–12 months 3 Meningococcal conjugate varies by region 6–12 months 1 Inactivated polio varies by region 6–12 months 3 Recombinant Hep B varies by region 6–12 months 3 Inactivated influenza + yearly 1-2 Live vaccines Measles seronegative adults 24 months 1-2 given together - Mumps + avoid if active Rubella + GVHD *Depends on national guidelines. | 340 | 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 64 and 65:
References 1. Petersdorf EW, Malkki
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 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?